CROSS-REFERENCE TO RELATED APPLICATIONS

[01] This application claims the benefit of U.S. Provisional Application No. 61/91 1 ,839, filed on December 4, 2013, which is incorporated by reference herein in its entirety.

FIELD OF THE INVENTION

[02] The invention relates to fermentative production of bioproducts and recovery of bioproducts from the fermentation medium, in particular with integration with grain ethanol production equipment and processes, and with conservation and recycle of resources and/or energy.

BACKGROUND

[03] Butanol is an important industrial solvent, with an annual global demand of about 6 to 8 million tons per year. It is used directly as a solvent and also is reacted to form derivatives like butyl acetate and butyl acrylate.

[04] Historically, butanol was produced by bacterial fermentation using a variety of renewable carbohydrate sources that included corn (maize), molasses, and cellulosic sugars. As oil supplies increased and prices fell during the mid-twentieth century, petrochemical processes became more economical and the renewable processes were abandoned.

There is much interest to rebuild a renewable butanol industry, but the economics have been limited by low product yields, high energy demand, and the cost of potential feedstocks. New processes that address each of these limitations with methods that greatly reduce energy consumption and enable the conversion of low cost feedstocks such as corn fiber would be desirable.

BRIEF SUMMARY OF THE INVENTION

[05] In one aspect, a method is provided for producing a bioproduct, including: (a) culturing a microorganism that produces the bioproduct in a bioreactor that contains a fermentable feedstock, wherein the microorganism ferments the feedstock to produce the bioproduct, thereby producing a fermentation broth that contains the bioproduct; (b) heating the fermentation broth; (c) distilling the heated fermentation broth under pressure (e.g., at a pressure that is higher than atmospheric pressure) to produce a vapor that contains the bioproduct, wherein the vapor that contains the bioproduct is separated from whole stillage; (d) condensing the vapor, thereby producing a condensate that comprises the bioproduct; and (e) recovering the bioproduct from the condensate. In some embodiments, the method further includes preparation of feedstock, including media formulation, prior to step (a). In some embodiments, the pressure distillation (step (c)) is performed at a pressure of about 14 psia to about 30 psia. In some embodiments, at least a portion of the whole stillage that is separated from the bioproduct-containing vapor is recovered and reused for production of additional bioproduct. For example, the whole stillage is the bottoms product of the distillation in step (c). In some embodiments, the whole stillage is recycled at the same temperature and pressure as the distillation in step (c). In one embodiment, the whole stillage is added to additional feedstock prior to introduction of the additional feedstock into a bioreactor. For example, the whole stillage may be used for the sterilization of additional feedstock (e.g., sterilization of feedstock after hydrolysis but prior to introduction into a bioreactor), at a temperature that is suitable to sterilize the additional feedstock. For example, the whole stillage may be at a temperature of about 100° C to about 130° C, e.g., about 1 10° C to about 120° C. In some embodiments, at least a portion of the whole stillage may be used to preheat the beer feed prior to distillation in step (c) and/or to preheat water which may be used to dilute the feedstock (e.g., grain, such as corn flour) prior to hydrolysis.

[06] In some embodiments, the fermentable feedstock includes grain, for example, corn, milo, barley, rice, and/or wheat, as well as other starch sources such as potatoes, cassava, and/or bamboo. In some embodiments, the grain starches may be hydrolyzed, for example, enzymatically. In one embodiment, the feedstock includes hydrolyzed corn mash.

[07] In some embodiments, the feedstock may be hydrolyzed (e.g., enzymatically hydrolyzed) to extract fermentable sugars, for example, hydrolyzed palm kernel cake (expeller).

[08] In some embodiments, the fermentable feedstock includes cane juice, molasses, sorghum based sugar streams, or corn syrup.

[09] In some embodiments, the fermentable feedstock includes whole stillage and/or thin stillage (e.g., concentrated thin stillage). For example, whole and/or thin stillage may contain lactic acid and/or glycerol, which may be utilized as a carbon source by the fermenting microorganism. [10] In some embodiments, the fermentable feedstock includes hydrolyzed cellulosic (e.g., lignocellulosic) biomass. Cellulosic (e.g., lignocellulosic) biomass may be hydrolyzed, for example, with acid and/or by liquefaction with one or more enzyme(s).

[11] In some embodiments, the bioproduct is an organic solvent. In one embodiment, the bioproduct is an alcohol, for example, butanol (e.g., n-butanol). In another embodiment, the bioproduct is crotyl alcohol (2-butenol). In one embodiment, the bioproduct is a ketone, for example, acetone. In some embodiments the bioproduct is isopropyl alcohol or ethanol.

[12] In some embodiments, the bioproduct is butanol and/or crotyl alcohol and the vapor produced via pressure distillation is an azeotropic vapor. In one embodiment, the azeotropic vapor contains water and about 25% (w/w) to about 55% (w/w) butanol and/or crotyl alcohol. In some embodiments, the microorganism that produces butanol and/or crotyl alcohol also produces acetone, and the vapor produced via pressure distillation contains butanol and/or crotyl alcohol, and acetone, for example, an azeotropic vapor that contains butanol and/or crotyl alcohol, and acetone. In one embodiment, the azeotropic vapor contains water and about 25% (w/w) to about 55% (w/w) butanol and/or crotyl alcohol, at up to about 20% (w/w) acetone. In some embodiments, the azeotropic vapor contains additional compounds, for example, acids and/or furans. In some embodiments, acetone is recovered with butanol and/or crotyl alcohol in the condensate that is produced from the bioproduct-containing vapor. In some embodiments, the azeotropic vapor further contains ethanol and/or other solvents such as isopropyl alcohol. For example, in some embodiments, the azeotropic vapor may contain up to about 5% (w/w) ethanol. In some embodiments, the ethanol and/or other solvents are recovered with butanol and/or crotyl alcohol, and acetone in the condensate that is produced from the bioproduct-containing vapor.

[13] In some embodiments of the methods herein, heat for heating the fermentation broth prior to pressure distillation is supplied from steam, e.g. directly from steam or indirectly through a heat exchanger.

[14] In some embodiments, condensing the vapor to produce a condensate that contains the bioproduct is conducted in one or more evaporators.

[15] In some embodiments, the condensate is conducted to a fractionating column for fractionation of bioproducts in the condensate. For example, from a condensate that contains butanol and/or crotyl alcohol, and acetone, acetone and a butanol and/or crotyl alcohol-containing liquid may be separated in the fractionating column. In one

embodiment, from a condensate that contains butanol and/or crotyl alcohol, acetone, and mixed solvents, acetone is removed from the top of the fractionating column, a butanol and/or crotyl alcohol-water mixture is removed from the bottom of the column, and a mixed solvent stream that contains ethanol is removed from a location that is between the top and the bottom of the column. In some embodiments, the mixed solvent stream may optionally be conducted to a "solvent flash column," in which at least a portion of the acetone is vaporized and sent back to the fractionating column. In some embodiments, the butanol and/or crotyl alcohol-containing liquid is conducted to a decanter, wherein the butanol and/or crotyl alcohol-containing liquid contains a light phase (e.g., containing 65% (w/w) to about 90% (w/w), or about 70% (w/w) to about 75% (w/w) butanol and/or crotyl alcohol) and a heavy phase (e.g., containing about 5% (w/w) to about 20% (w/w) butanol and/or crotyl alcohol), wherein a greater amount of butanol and/or crotyl alcohol segregates to the light phase than the heavy (aqueous) phase. In some embodiments, the heavy phase is recycled and included in the pressure distillation of fermentation broth to produce a butanol and/or crotyl alcohol-containing vapor. In some embodiments, the light phase is conduced to a butanol and/or crotyl alcohol purification column for recovery of butanol and/or crotyl alcohol from the light phase.

[16] In some embodiments, the condensate is conducted to a decanter wherein the condensate contains a light phase (e.g., containing about 65% (w/w) to about 90% (w/w), or about 70%) (w/w) to about 75% (w/w) butanol and/or crotyl alcohol) and a heavy phase (e.g., containing about 5% (w/w) to about 20% (w/w) butanol and/or crotyl alcohol), wherein a greater amount of butanol and/or crotyl alcohol segregates to the light phase than the heavy (aqueous) phase. In some embodiments, the heavy phase is recycled and included in the pressure distillation of fermentation broth to produce a butanol and/or crotyl alcohol-containing vapor. In some embodiments, the light phase is conducted to a fractionating column for fractionation of bioproducts in the light phase. For example, from a light phase that contains butanol and/or crotyl alcohol and acetone, acetone and a butanol and/or crotyl alcohol-containing liquid may be separated in the fractionating column. The butanol and/or crotyl alcohol-containing liquid may be conducted to a butanol and/or crotyl alcohol purification column for recovery of butanol and/or crotyl alcohol.

[17] Typically, whole stillage includes liquid and unfermented feedstock solids. Liquid may be separated (e.g., at least a portion of the liquid) from the whole stillage, thereby producing liquid thin stillage and wet cake solids. In one embodiment, the thin stillage is separated from whole stillage by centrifugation. In some embodiments, the thin stillage is concentrated (e.g., via an evaporation process) to produce a syrup. In some embodiments, heat produced from the condensation of the bioproduct-containing vapor is used for concentration (e.g., evaporation) of thin stillage. In some embodiments, syrup produced from concentration of thin stillage is incorporated into an animal feed product. In one embodiment, the syrup is mixed with wet cake solids from whole stillage prior to incorporation into the animal feed product. The animal feed product may be sold "wet" (e.g., about 50% (w/w) to about 80%> (w/w) moisture), or may be dried (e.g., about 10%> (w/w) or less moisture). In some embodiments, the animal feed product includes DDGS (dried distillers grains with soluble) with at least about 40%> (w/w) (e.g., about 40%> (w/w) to about 50%) (w/w)) protein.

[18] In some embodiments, whole stillage is recovered from the pressure distillation process and included in a hydrolysis mixture to produce hydro lyzed cellulosic (e.g., lignocellulosic) biomass. . In some embodiments, the microorganism(s) in the bioreactor consume(s) at least a portion of the whole stillage (e.g., fiber in the whole stillage) during the fermentation process. In some embodiments, pressure distillation of the heated fermentation broth (e.g., at elevated temperature and/or reduced pH) provides a

pretreatment effect, increasing the ability of the whole stillage (e.g., fiber in the whole stillage) to be consumed by the microorganism.

[19] In some embodiments, whole stillage is recovered from the pressure distillation process and included in the fermentation medium in the bioreactor.

[20] In some embodiments, thin stillage is separated from whole stillage solids and concentrated (e.g., in one or more evaporators), thereby producing concentrated thin stillage (e.g. , a syrup), and a vapor that contains primarily water is recovered and condensed to produce a process condensate. The process condensate may be used, for example, as liquid for hydrolysis of feedstock and/or as liquid in the fermentation medium in the bioreactor and/or as a liquid used in a process scrubber to recover solvents from vapor streams.

[21] In another aspect, a method is provided for producing butanol and/or crotyl alcohol (e.g., n-butanol and/or crotyl alcohol), including: (a) culturing a microorganism that produces butanol and/or crotyl alcohol, and acetone, in a bioreactor that comprises fermentable feedstock, wherein the microorganism ferments the feedstock, thereby producing a fermentation broth that comprises butanol and/or crotyl alcohol, and acetone; (b) heating the fermentation broth; (c) producing a first vapor that includes butanol and/or crotyl alcohol, and acetone, wherein the first vapor is separated from whole stillage; (d) separating a butanol and/or crotyl alcohol-containing liquid and an acetone-containing second vapor from the first vapor in a distillation column and (e) recovering butanol and/or crotyl alcohol from the butanol and/or crotyl alcohol-containing liquid.

[22] In some embodiments, the method further includes preparation of feedstock, including media formulation, prior to step (a).

[23] In some embodiments, the first vapor includes about 40% (w/w) to about 70% (w/w) water.

[24] In some embodiments, step (c) includes distillation (e.g., pressure distillation), for example, but not limited to, a pressure of about 14 psia to about 30 psia. In some embodiments, step (c) includes evaporation.

[25] In some embodiments, at least a portion of the whole stillage that is separated from the bioproduct-containing vapor is recovered and reused for production of additional bioproduct. In some embodiments, the whole stillage is the bottoms product of a distillation process in step (c). In some embodiments, step (c) includes pressure distillation and the whole stillage is recycled at the same temperature and pressure as that at which the pressure distillation is conducted. In one embodiment, the whole stillage is added to additional feedstock prior to introduction of the additional feedstock into a bioreactor. For example, the whole stillage may be used for the sterilization of additional feedstock (e.g., sterilization of feedstock after hydrolysis but prior to introduction into a bioreactor), at a temperature that is suitable to sterilize the additional feedstock. For example, the whole stillage may be at a temperature of about 100° C to about 130° C, e.g., about 1 10° C to about 120° C. In some embodiments, at least a portion of the whole stillage may be used to preheat the beer feed prior to distillation in step (c) and/or to preheat water which may be used to dilute the feedstock (e.g., grain, such as corn flour) prior to hydrolysis.

[26] In some embodiments, the fermentable feedstock includes grain, for example, corn, milo, barley, rice, and/or wheat, as well as other starch sources such as potatoes, cassava, and/or bamboo. In some embodiments, the grain starches may be hydrolyzed, for example, enzymatically. In one embodiment, the feedstock includes hydrolyzed corn mash.

[27] In some embodiments, the fermentable feedstock includes cane juice, molasses, sorghum based sugar streams, or corn syrup.

[28] In some embodiments, the fermentable feedstock includes whole stillage and/or thin stillage (e.g., concentrated thin stillage). For example whole and/or thin stillage may contain lactic acid and/or glycerol, which may be utilized as a carbon source by the fermenting microorganism. [29] In some embodiments, the fermentable feedstock includes hydrolyzed cellulosic (e.g., lignocellulosic) biomass. Cellulosic (e.g., lignocellulosic) biomass may be

hydrolyzed, for example, with acid and/or by liquefaction with one or more enzyme(s).

[30] In some embodiments, the first vapor is an azeotropic vapor. In one embodiment, the azeotropic vapor contains water and about 25% (w/w) to about 55% (w/w) butanol and/or crotyl alcohol and up to about 20% (w/w) acetone. In some embodiments, the azeotropic vapor contains additional compounds, for example, acids and/or furans.

[31] In some embodiments, the second vapor includes about 70%> (w/w) to 100% (w/w) acetone.

[32] In some embodiments, the method further includes: (f) condensing the second vapor, thereby producing a condensate that comprises acetone. In some embodiments, condensing the second vapor is conducted in one or more evaporators. In one embodiment, the one or more evaporators are coupled to a compressor (e.g., thermal or mechanical vapor recompression).

[33] In some embodiments, step (c) includes distillation (e.g., pressure distillation), and energy for the distillation column in step (d) and/or for the evaporation process that is conducted in the one or more evaporators is supplied by the distillation system of step (c).

[34] In some embodiments, the first vapor further includes ethanol and/or one or more other solvent(s). In some embodiments, the second vapor further includes ethanol and/or one or more other solvent(s). In some embodiments, the ethanol and/or one or more other solvent(s) is (are) recovered with acetone in the condensate.

[35] In some embodiments, the butanol and/or crotyl alcohol-containing liquid is conducted to a decanter, wherein the butanol and/or crotyl alcohol-containing liquid includes a light phase and a heavy phase, wherein a greater amount of butanol and/or crotyl alcohol segregates to the light phase than the heavy (aqueous) phase. In some

embodiments, step (c) includes a distillation (e.g. , pressure distillation) system, and the heavy phase is returned to the distillation system for production of the first vapor. In some embodiments, the light phase is conducted to a butanol and/or crotyl alcohol purification column, wherein butanol and/or crotyl alcohol is recovered from the light phase.

[36] Typically, the whole stillage includes liquid and unfermented feedstock solids.

Liquid may be separated (e.g., at least a portion of the liquid) from the whole stillage, thereby producing liquid thin stillage and wet cake solids. In one embodiment, the thin stillage is separated from whole stillage by centrifugation. In some embodiments, the thin stillage is concentrated (e.g., via an evaporation process) to produce a syrup. In some embodiments, heat produced from the condensation of the bioproduct-containing vapor is used for concentration (e.g., evaporation) of thin stillage. In some embodiments, syrup produced from concentration of thin stillage is incorporated into an animal feed product. In one embodiment, the syrup is mixed with wet cake solids from whole stillage prior to incorporation into the animal feed product. The animal feed product may be sold "wet" (e.g., about 50% (w/w) to about 80% (w/w) moisture), or may be dried (e.g., about 10%> (w/w) or less moisture). In some embodiments, the animal feed product includes DDGS with at least about 40%> (w/w) (e.g., about 40%> (w/w) to about 50%> (w/w)) protein.

[37] In some embodiments, whole stillage is recovered and included in a hydrolysis mixture to produce hydrolyzed cellulosic (e.g., lignocellulosic) biomass. In some embodiments, whole stillage is included in the fermentation medium in the bioreactor. In some embodiments, the microorganism(s) in the bioreactor consume(s) at least a portion of the whole stillage (e.g., fiber in the whole stillage) during the fermentation process. In some embodiments, pressure distillation of the heated fermentation broth (e.g., at elevated temperature and/or reduced pH) provides a pretreatment effect, increasing the ability of the whole stillage (e.g., fiber in the whole stillage) to be consumed by the microorganism.

[38] In some embodiments, thin stillage is separated from whole stillage solids and concentrated (e.g., in one or more evaporators), thereby producing concentrated thin stillage (e.g. , a syrup), and a vapor that contains primarily water is recovered and condensed to produce a process condensate. The process condensate may be used, for example, as liquid for hydrolysis of feedstock and/or as liquid in the fermentation medium in the bioreactor and/or as a liquid used in a process scrubber to recover solvents from vapor streams.

[39] In another aspect, a method is provided for producing a bioproduct of interest, including: (a) culturing a first microorganism in a first fermentation process, wherein the first microorganism produces a first bioproduct and one or more byproducts in a first fermentation broth; and (b) conducting a second fermentation process with a second microorganism, wherein the second microorganism produces a second bioproduct in a second fermentation broth, wherein the one or more byproducts of the first fermentation process are provided to the second fermentation and utilized as a carbon source and/or nutrients for growth of the second microorganism in the second fermentation process.

[40] In some embodiments, the first microorganism is an ethanol-producing

microorganism (e.g., yeast) and the first bioproduct is ethanol.

[41] In some embodiments, the second bioproduct is an organic solvent, such as, for example, an alcohol. In one embodiment, the second bioproduct is butanol (e.g., n-butanol) and/or crotyl alcohol, and in some embodiments, the second microorganism further produces acetone and/or isopropanol. In some embodiments, the second microorganism is a Clostridium species.

[42] In some embodiments, the first fermentation broth includes one or more components that serve as a carbon source for the second fermentation process, for example,

carbohydrate(s) {e.g., sucrose, xylose, arabinose, mannose, glucose, fructose, galactose, starch), glycerol, organic acid(s) {e.g., acetic acid, lactic acid), fatty acid(s) {e.g., C4-C18), and/or other metabolic byproduct(s) of the first fermentation.

[43] In some embodiments, the first fermentation broth includes one or more

carbohydrate molecules that the first microorganism does not metabolize. In one embodiment, carbohydrate molecules in the first fermentation broth that the first microorganism does not metabolize include xylose and/or arabinose. In one embodiment, carbohydrate molecules in the first fermentation broth that the first microorganism does not metabolize include pentose sugars from hemicellulose.

[44] In some embodiments, the first fermentation broth includes residual carbohydrate molecules that are not metabolized in the first fermentation process, for example, glucose, mannose, cellulose, hemicellulose, and/or starch.

[45] In some embodiments, the first fermentation process includes culturing the first microorganism in a first culture medium that includes grain, molasses, and/or hydrolyzed cellulosic biomass. In some embodiments, the first culture medium includes grain, for example, corn, milo, barley, rice, and/or wheat, as well as other starch sources, such as potatoes, cassava, and/or bamboo. In some embodiments, the grain starches may be hydrolyzed, for example, enzymatically. In one embodiment, the first culture medium includes hydrolyzed corn mash, for example, produced by enzymatic hydrolysis. In one embodiments, the first culture medium includes a hydrolysate of cellulosic biomass, for example, produced by acid hydrolysis and/or enzymatic liquefaction of the cellulosic biomass.

[46] In some embodiments, at least a portion of the first bioproduct is removed from the first fermentation broth prior to inclusion of the first fermentation broth in the second fermentation process. In one embodiment, the first microorganism is yeast and the first bioproduct is ethanol. For example, at least about 95% {e.g., about 95% to 100%) of the ethanol may be removed prior to inclusion of the first fermentation broth in the second fermentation process. [47] In some embodiments, the method further includes: heating the second fermentation broth; and producing a vapor that includes the second bioproduct, wherein the vapor that includes the second bioproduct is separated from whole stillage. In one embodiment, the vapor is produced by distillation (e.g., pressure distillation). In another embodiment, the vapor is produced by evaporation. In some embodiments, the method further includes condensing the vapor, thereby producing a condensate that comprises the second bioproduct. In some embodiments, the method further includes recovering the second bioproduct from the condensate. In some embodiments, at least a portion of the whole stillage is recovered and added to feedstock (e.g., hydro lyzed grain) prior to use of the feedstock in the first and/or second fermentation process, wherein the temperature of the whole stillage is suitable to sterilize the feedstock. In some embodiments, at least a portion of the whole stillage is recovered and included in the fermentation medium in the second fermentation process. In some embodiments, at least a portion of the liquid is separated from the whole stillage, thereby producing liquid thin stillage, and wherein the thin stillage is used as liquid for fermentation in the first and/or second fermentation process. In some embodiments, at least a portion of the liquid is separated from the whole stillage, thereby producing liquid thin stillage, the thin stillage is concentrated, thereby producing concentrated thin stillage and a process condensate that includes primarily water, and the process condensate is used as liquid for fermentation in the first and/or second fermentation process.

[48] In another aspect, a continuous reflux distillation system is provided for separating acetone from other solvents (e.g., separation of acetone from ethanol or mixed solvents). The distillation system includes: (a) a feed that includes acetone, water and other solvents; (b) a first distillation column that includes a top portion and a bottom portion; (c) an inlet through which feed is introduced into the first distillation column; and (d) a side draw that is at a location between the top portion and the bottom portion of the column and at a location that is higher in the column than the feed inlet. When the first distillation column is operated under conditions that are suitable for distillation and separation of acetone from the other solvents, acetone-rich vapor exits through an outlet in the top portion of the column and a mixed solvent stream through the side draw. The mixed solvent stream includes a lower concentration of acetone than the acetone-rich vapor than exits through the top portion of the column. In some embodiments, the acetone-rich vapor is condensed and a portion of the liquid is recycled to the top portion of the column as "reflux." In some embodiments, the location of the side draw is optimized for removal of ethanol or mixed solvents. In one embodiment, the location of the side draw is configured at a location where ethanol preferentially accumulates in the column. In some embodiments, the acetone-rich vapor that exits through the top portion of the column contains a high concentration of acetone (e.g., 99% or greater) and impurities such as water, C0 ₂ , and/or ammonia. In some embodiments, the feed includes butanol and/or crotyl alcohol, and the butanol and/or crotyl alcohol exits through an outlet in the bottom portion of the first distillation column in a bottoms product composition. In some embodiments, the feed includes ethanol, and ethanol exits the first distillation column in the mixed solvent stream. In some embodiments, the first distillation column is operated at a pressure of about 6 psia to about 15 psia. In some embodiments, the feed includes acetone, water, ethanol, and other solvents. In some embodiments, the feed includes acetone, water, ethanol, butanol and/or crotyl alcohol, and other solvents.

[49] In some embodiments, the distillation system includes a reboiler to provide heat for the distillation. In some embodiments, the distillation system includes (e) a second distillation column that includes a top portion and a bottom portion. The mixed solvent stream that exits the first distillation column through the side draw of the first distillation column includes acetone and is conducted to the top portion of the second distillation column. The second distillation column is operated under conditions that are suitable for distillation and separation of acetone from the mixed solvent stream, acetone-rich vapor exits through an outlet in the top portion of the second distillation column, and a mixed solvent stream exits through an outlet in the bottom portion of the second distillation column. The mixed solvent stream that exits through the bottom of the second distillation column includes a lower concentration of acetone than the mixed solvent stream that exits through the side draw of the first distillation column. In some embodiments, the acetone- rich vapor that exits through the top portion of the second distillation column is recycled to the first distillation column and enters the first distillation column through an inlet that is at a location that is at or higher than the location of the side draw. In some embodiments, the second distillation column is operated at a pressure that is the same as or substantially the same as the pressure of the first distillation column, e.g., about 6 psia to about 15 psia. In some embodiments, the first distillation column and the second distillation column are operated as a continuous system.

[50] In another aspect, a method is provided for separating acetone from other solvents. The method includes (a) conducting a feed that includes acetone, water, and other solvents through an inlet into a first distillation column that includes a top portion, a bottom portion, and a side draw that is at a location that is higher in the column than the feed inlet; (b) operating the first distillation column under conditions that are suitable for distillation and separation of the acetone from the other solvents; and (c) recovering acetone-rich vapor through an outlet in the top portion of the column and recovering a mixed solvent stream that comprises a lower concentration of acetone and the acetone -rich vapor through the side draw, wherein the first distillation column is operated as a continuous reflux distillation system. In some embodiments, the feed includes butanol and/or crotyl alcohol, and the method includes recovering butanol and/or crotyl alcohol through an outlet in the bottom portion of the first distillation column in a bottoms product composition. In some embodiments, the feed includes ethanol, and wherein the mixed solvent stream comprises ethanol. In some embodiments, the first distillation column is operated at a pressure of about 6 psia to about 15 psia. In some embodiments, the first distillation column further includes a reboiler, and heat for the distillation is provided to the first distillation column by the reboiler.

[51] In some embodiments, the method further includes: (d) conducting the mixed solvent stream to a second distillation column that includes a top portion and a bottom portion, wherein the mixed solvent stream that exits through the side draw of the first distillation column includes acetone. The second distillation column is operated under conditions that are suitable for distillation and separation of acetone from the mixed solvent stream. Acetone-rich vapor exits through an outlet in the top portion of the second distillation column and a mixed solvent stream exits through an outlet in the bottom portion of the second distillation column, wherein the mixed solvent stream that exits the bottom of the second distillation column includes a lower concentration of acetone than the mixed solvent stream that exits through the side draw of the first distillation column. In some embodiments, acetone vapor that exits through the top portion of the second distillation column is recycled to the first distillation column and enters the first distillation column at an inlet that is at a location that is at or higher than the location of the side draw.

BRIEF DESCRIPTION OF THE DRAWINGS

[52] Figure 1 schematically depicts one embodiment of a bioproduct recovery process as described herein.

[53] Figure 2 schematically depicts one embodiment of a bioproduct recovery process as described herein. [54] Figure 3 schematically depicts one embodiment of a bioproduct recovery process as described herein.

[55] Figure 4 schematically depicts one embodiment of a bioproduct production and recovery process as described herein.

[56] Figure 5 schematically depicts one embodiment of a bioproduct production and recovery process as described herein.

[57] Figure 6 schematically depicts one embodiment of an integrated process for production and recovery of two bioproducts as described herein.

[58] Figure 7 schematically depicts one embodiment of an integrated process for production and recovery of two bioproducts as described herein.

[59] Figure 8 schematically depicts one embodiment of an acetone distillation column with mixed solvent side draw as described herein.

[60] Figure 9 schematically depicts one embodiment of an acetone distillation column with mixed solvent side draw as described herein.

[61] Figure 10 schematically depicts one embodiment of a bioproduct recovery process as described herein.

[62] Figure 11 schematically depicts one embodiment of a bioproduct recovery process as described herein.

[63] Figure 12 schematically depicts one embodiment of a bioproduct recovery process as described herein.

[64] Figure 13 schematically depicts one embodiment of a full process overview that includes a bioproduct recovery process and whole stillage recycle.

[65] Figure 14 schematically depicts one embodiment of a full process overview that includes a bioproduct recovery process and whole stillage recycle.

[66] Figure 15 schematically depicts one embodiment of an integrated process for production and recovery of two bioproducts as described herein.

DETAILED DESCRIPTION

Definitions

[67] "A," "an" and "the" include plural references unless the context clearly dictates otherwise.

[68] "Azeotrope" refers to a mixture of two or more liquids which, when boiled, have the same vapor and liquid compositions. Neither component is concentrated in the vapor phase. A "Positive Azeotrope" occurs when the azeotrope boiling point is lower (colder) than either of the pure component boiling points. For example, a mixture of 55 wt% n-butanol and 45 wt% water forms a positive azeotrope when distilled at atmospheric pressure, boiling at about 92.4 deg C. The pure-component, atmospheric boiling points are 117.8 deg C for n-butanol and 100 deg C for water. Similarly, certain mixtures of crotyl alcohol and water form a positive azeotrope that boils at about 94.2 deg C. The two isomers of crotyl alcohol have atmospheric boiling points of about 121-123 deg C.

[69] "Bio fuel" refers to fuel molecules (e.g., butanol, acetone, and/or ethanol) produced biologically by a microorganism, e.g., in a microbial fermentation process.

[70] "Biobutanol" refers to butanol produced biologically by a microorganism, e.g., in a microbial fermentation process.

[71] n-Butanol (1-butanol) is also referred to as "butanol" herein.

[72] "Feedstock" refers to a substance that can serve as a source of carbon to support microbial growth in a fermentation process. In some embodiments, the feedstock must be pretreated to release sugar molecules, which may serve as a carbon source. In one embodiment, the feedstock is hydrolyzed to release 5- and/or 6-carbon sugar molecules.

[73] "Deconstruction" refers to mechanical, chemical, and/or biological degradation of biomass into to render individual components (e.g. , cellulose, hemicellulose) more accessible to further pretreatment processes, for example, a process to release monomeric and oligomeric sugar molecules, such as acid hydrolysis.

[74] "Conditioning" refers to removal of inhibitors of microbial growth and/or biofuel production from a feedstock or pretreated feedstock (e.g., a hydro lysate produced by hydrolysis of a feedstock).

[75] "Titer" refers to amount of a substance produced by a microorganism per unit volume in a microbial fermentation process. For example, biobutanol titer may be expressed as grams of butanol produced per liter of solution.

[76] "Yield" refers to amount of a product produced from a feed material (for example, sugar) relative to the total amount that of the substance that would be produced if all of the feed substance were converted to product. For example, biobutanol yield may be expressed as % of biobutanol produced relative to a theoretical yield if 100% of the feed substance (for example, sugar) were converted to biobutanol.

[77] "Sterilize" and "sterilization" refer to substantial or complete elimination and/or destruction of contaminating microorganisms. [78] "Productivity" refers to the amount of a substance produced by a microorganism per unit volume per unit time in a microbial fermentation process. For example, biobutanol productivity may be expressed as grams of butanol produced per liter of solution per hour.

[79] "Wild-type" refers to a microorganism as it occurs in nature.

[80] "Biomass" refers to cellulose- and/or starch-containing raw materials, including but not limited to wood chips, corn stover, corn fiber, ground whole corn plant, grasses, forages, prairie-grass, tubers, roots, grape pomace, cobs, sugar-containing raw materials (e.g., molasses, fruit materials, sugar cane, or sugar beets), wood, bagasse, and plant residues.

[81] "Starch" refers to any starch-containing materials. In particular, the term refers to various plant-based materials, including but not limited to grains, cereals, wheat, barley, potato, sweet potato, tapioca, corn, maize, cassava, milo, rye, brans, whole ground corn, and bamboo. In general, the term refers to any material comprised of the complex

polysaccharide carbohydrates of plants, comprised of amylose, and amylopectin, with the formula wherein "x" can be any number.

[82] "ABE fermentation" refers to production of acetone, butanol, and ethanol by a fermenting microorganism.

[83] "Advanced biofuels" are high-energy liquid transportation fuels derived from low nutrient input/high per acre yield crops, agricultural or forestry waste, or other sustainable biomass feedstocks including algae.

[84] The term "culturing" refers to growing a population of cells, e.g., microbial cells, under suitable conditions for growth, in a liquid or solid medium.

[85] "Whole stillage" refers to unfermented solid material and associated liquid that remains after fermentation and removal of fermentation broth.

[86] "Thin stillage" refers to the liquid portion of whole stillage.

[87] "Stripping" refers to transferring at least a portion of a volatile component from a liquid stream into a gaseous stream.

[88] "Rectifying" refers to concentrating one or more volatile compounds in a distillation column or evaporator.

[89] "Beer" refers to fermentation broth.

[90] "Solvent" refers to a liquid or gas produced by a microorganism that is capable of dissolving a solid or another liquid or gas. Nonlimiting examples of solvents produced by microorganisms include n-butanol, acetone, ethanol, crotyl alcohol (2-butenol), acetic acid, isopropanol, n-propanol, methanol, formic acid, 1 ,4-dioxane, tetrahydrofuran, acetonitrile, dimethylformamide, and dimethyl sulfoxide.

[91] A "protic" solvent contains dissociable H ⁺ , for example a hydrogen atom bound to an oxygen atom as in a hydroxyl group or a nitrogen atom as in an amino group. A protic solvent is capable of donating a proton (H ). Conversely, an "aprotic" solvent cannot donate H ⁺ .

Exemplary embodiments

[92] Exemplary, non-limiting embodiments of the methods and systems as described herein are depicted in the drawings. The drawings are directed generally to a process in which butanol is produced in a microbial fermentation process and purified from the resulting fermentation broth ("beer"). In some embodiments, the microorganism also produces acetone, ethanol, and/or other solvents. In some embodiments, the fermentation is an "ABE" fermentation in a microorganism that produces acetone, butanol, and ethanol (for example, an ABE-producing bacterium of the Clostridium genus or a microorganism that has been engineered, for example, by recombinant technology, to produce these products.) The drawings depict separation of these other bioproducts from butanol. The processes described herein may be adapted for purification of other bioproducts of interest, provided that such bioproducts are separable from the fermentation medium, with recycle of whole stillage and other process parameters as described herein, for example, separation of a vapor phase that contains the bioproduct(s) of interest from the whole stillage, and purification of the bioproduct(s) from the vapor phase. In some embodiments, crotyl alcohol (2-butenol) is produced in addition to or instead of butanol in a microbial fermentative process as described herein. Crotyl alcohol may be purified from the fermentation broth in a similar manner to butanol as described herein. In any of the embodiments of methods or systems described herein and/or depicted in the drawings, crotyl alcohol may be produced in a fermentation and recovered from fermentation broth in addition to or instead of butanol.

[93] Some non-limiting examples of advantageous features of exemplary embodiments of the methods and systems described herein are as follows. Other advantages will be apparent from the description herein.

1. Using pressure distillation, and recovering the heat in evaporators.

2. A three column bioproduct {e.g., butanol and/or crotyl alcohol) recovery system (low capital expenditure).

3. Direct (hot) recycle of whole stillage, which is useful for achieving sterilizing temperatures {e.g., 100 °C-121°C) for additional feedstock material without additional heat exchangers or jet cookers.

4. Recycling the stillage, which contains cooked feedstock (e.g., corn) fiber,

allowing gentle 'pretreatment' of the fiber. Upon recycling, enzymes may be added to digest the fibers and microorganisms (e.g., microorganisms that can consume glucose and xylose) can consume the sugars in a microbial fermentation as disclosed herein. In some embodiments, enzymatic digestion is not required for microorganism utilization of the whole stillage as a feedstock in a

fermentation process.

5. Integration of a bioproduct (e.g., butanol and/or crotyl alcohol) production

process with corn ethanol or other prior fermentation, transferring byproducts (e.g. , lactic acid, glycerol) from the first fermentation process to a second fermentation for consumption by the second bioproduct-producing

microorganism.

[94] In some embodiments of the methods and systems disclosed herein, the pH of the beer may be reduced prior to distillation. Advantages of the pH reduction may include, but are not limited to, reduction of mineral fouling in the distillation column and facilitation of low-severity acid hydrolysis during distillation, pre-treating the fibers that are present. In some embodiments, a reduced-fiber animal feed product may be advantageously produced, by digesting a portion of the corn fiber. In some embodiments, whole stillage recycling and fiber digestion may advantageously improve corn oil recovery, as more corn oil will be released from the corn germ and transferred to thin stillage, where it may be recovered. In some embodiments, reducing the pH of the beer (and thus of whole stillage and thin stillage) may facilitate recovery of residual acetic acid and butyric acid from the thin stillage, resulting in improved feed product flavor of downstream products such as animal feed. These compounds may alternately or additionally be converted to acetone, butanol, crotyl alcohol, and/or other downstream chemical products.

[95] Fermentation systems and processes for fermentative production of bioproducts are well known in the art. For the fermentations described herein, a fermentable feedstock may be any carbon-containing material that serves as a carbon source for a microbial fermentation to produce the bioproduct(s) of interest. Non-limiting examples of feedstock materials that may be used in the fermentations described herein include grain (e.g., hydrolyzed grain), molasses, hydrolyzed cellulosic (e.g., lignocellulosic) biomass, organic acids, glycerol, and/or combinations thereof. One example of a fermentable feedstock for use in the fermentations described herein is hydrolyzed grain, such as hydrolyzed corn mash. In some embodiments, corn grain is milled, then slurried with water to create "mash." Enzymes are added to the mash and this mixture is then cooked to hydrolyze the starch into sugars (e.g., glucose) that are suitable for fermentation by a microorganism. In some embodiments, whole stillage is recycled from the fermentation, as described herein, and added to the corn mash prior to, during, or after hydrolysis, e.g., at a temperature that is suitable to sterilize the feedstock prior to its introduction into a bioreactor for microbial fermentation.

[96] The drawings herein depict schematically production and recovery of butanol and other solvents. In any of the drawings that specify purification of butanol, crotyl alcohol may be substituted. Recovery of crotyl alcohol from a fermentation broth will proceed through the same steps and processes as those exemplified in the drawings for butanol. For example, a "butanol column" may be a "crotyl alcohol column" for purification of butanol, and a "butanol" product may be a "crotyl alcohol product."

[97] One option for purification of butanol from a microbial fermentation is shown in Figure 10. Warm fermentation medium ("beer feed") is introduced above a stripping section in a distillation column ("beer stripper/rectifier"). The beer is heated, for example, to a temperature of about 75° C to about 105° C. In some embodiments, the beer is distilled under pressure. For example, a pressure of about 14 psia to about 30 psia may be employed. In one embodiment, whole stillage is recycled from the bottom of the beer column and heat from the whole stillage is transferred to the warm beer entering the column, for example, through a heat exchanger. The whole stillage may be heated by pressure employed in the pressure distillation, which causes water to boil at a temperature greater than 100° C, producing steam. In another embodiment, heat is supplied to the warm beer feed entering the column from steam, e.g. directly from steam or indirectly through a heat exchanger. In a further embodiment, a portion of whole stillage is recycled to a hydrolysis (e.g. , enzymatic starch liquefaction) system, and the portion of the whole stillage that is not recycled is removed for processing (e.g. , centrifugation) and incorporation into downstream product(s) (e.g., animal feed). The portion of the whole stillage that is not recycled may be passed through a heat exchanger that (i) cools the stillage; and (ii) heats up process liquid (e.g., water), for example, that is produced by evaporators downstream from the beer distillation column.

[98] A vapor exits the top of the column. In some embodiments, the vapor is an azeotrope of butanol and water. In some embodiments, the vapor may also include acetone, ethanol, and/or other solvents. [99] The vapor is condensed, for example, in one or more evaporators. Butanol may be purified from the condensate. The condensate may be conducted to a decanter, either before or after a second distillation ("acetone column"). An embodiment in which the decanter is located downstream from the second distillation is shown in Figure 10. An alternate embodiment in which the decanter is located upstream from the second distillation is shown in Figure 11.

[100] In embodiments in which other solvents, such as acetone and/or ethanol, are included in the condensate, the condensate may be directed to a distillation column, termed "acetone column" in Figures 10-14, which may separate acetone, ethanol, and/or mixed solvents from butanol (e.g., butanol and/or and water, and optionally other soluble components). In some embodiments, a vapor that contains acetone, ethanol, and/or mixed solvents exits the top of the column and liquid that contains butanol exits the bottom of the column. In other embodiments, an acetone containing vapor exits the top of the column, a liquid that contains butanol exits the bottom of the column, and a mixed solvent stream that contains ethanol is removed at a location that is between the top and the bottom of the column. In some embodiments, the mixed solvent stream may optionally be conducted to a "solvent flash column," in which at least a portion of the acetone is vaporized and sent back to the acetone column.

[101] In some embodiments, the acetone column is operated in a pressure range of about 6 psia to about 15 psia, e.g., partial vacuum up to atmospheric pressure. The acetone column may be heated with a reboiler. In some embodiments, the reboiler may be heat-integrated with other equipment and/or process streams. Mixed solvents may be removed as a side draw. In some embodiments, mixed solvents may be removed directly or may be passed into a "solvent flash column" that strips out most of the acetone from the mixed solvents. The solvent flash column may be heated, for example, directly or indirectly with steam. Vapor that exits the top of the solvent flash column may be returned to the acetone column at the same location or higher (e.g., closer to the top of the column) than the location of the side draw.

[102] In the embodiment depicted in Figure 10, the butanol-containing liquid (e.g., primarily butanol and water) may be conducted to a decanter, which separates the butanol- containing liquid into a light phase and a heavy phase, wherein a greater amount of butanol segregates to the light phase than the heavy phase. In some embodiments, the light phase contains about 65% (w/w) to about 90% (w/w), or about 70% (w/w) to about 75% (w/w) butanol and the heavy phase contains about 5% (w/w) to about 20% (w/w) butanol. [103] In some embodiments, the light phase is conducted to a butanol purification column, in which butanol is separated from other liquid(s) (e.g., water). The butanol product, which may have a purity of about 99 to about 99.9%, exits the bottom of the butanol purification column.

[104] In some embodiments, the heavy phase from the decanter is combined with beer entering the beer stripper column, for recovery of additional butanol. In some

embodiments, the heavy phase may be added at a position toward the top of the beer stripping column that is sufficient to provide some cooling and to concentrate (rectify) the solvents.

[105] In other embodiments, the heavy phase may be used as a cleaning solution, e.g., in pipes, heat exchangers, and/or fermenters.

[106] Alternately, the condensate from the evaporators may be conducted to a decanter before the acetone column, as shown in Figure 11. The condensate is conducted to a decanter. The decanter contains a light phase (e.g., containing about 65% (w/w) to about 90%) (w/w), or about 70%> (w/w) to about 75% (w/w) butanol) and a heavy phase (e.g., containing about 5% (w/w) to about 20%> (w/w) butanol), with a greater amount of butanol segregating to the light phase than the heavy (aqueous) phase. In some embodiments, the heavy phase is recycled and included in the distillation (e.g., pressure distillation) of fermentation broth to produce a butanol-containing vapor in the beer stripper/rectifier. The light phase is conducted to a fractionating column for fractionation of bioproducts in the light phase. For example, from a light phase that contains butanol and acetone, acetone and a butanol-containing liquid may be separated in the fractionating column. The butanol- containing liquid may be conducted to a second decanter, followed by purification of the butanol from the light phase in a butanol purification column for recovery of butanol. The heavy phase from the second decanter may be recycled and included in the distillation (e.g., pressure distillation) of fermentation broth to produce a butanol-containing vapor in the beer stripper/rectifier.

[107] One embodiment of a larger overview of the process depicted in Figure 10 is shown in Figure 13. Figure 13 shows processing of grain (e.g., corn, milo) with water to produce a slurry mix, followed by enzymatic liquefaction to create a "mash." The mash is combined with a microbial seed culture in one or more bioreactor(s) to produce the bioproduct of interest (e.g., butanol and/or other solvent(s)). The fermentation broth is conducted to a beer well and then into a beer stripping column as described above. The bioproduct(s) of interest (e.g. , butanol) may be purified from the vapor produced in the beer stripping column, as described above.

[108] As shown in Figure 13, whole stillage may be recycled from the bottom of the beer stripping column. The whole stillage may be added to hydrolyzed grain, providing heat for sterilization of the hydrolyzed mash prior to introduction into the bioreactor(s). The whole stillage (e.g., at a temperature of about 100° C to about 150° C) may be added to hydrolyzed mash after hydrolysis, e.g., rendering a hydrolysate at a temperature of about 100° C to about 1 15° C. This may serve to sterilize the hydrolysate prior to introduction into the fermenter(s) In some embodiments, about 50% to about 90% of the total blend is from whole stillage. The blend may then be conducted to the fermenter(s). Whole stillage may also be conducted to a device (e.g., a centrifuge, screw-press, hydrocyclone, or static screen) for separation of liquid (e.g., thin stillage) from whole stillage solids. Thin stillage may be concentrated to produce a syrup. Whole stillage solids may be recovered and used for production of an animal feed product, optionally in combination with the thin stillage concentrate. A process condensate (e.g., primarily water) may be recovered as the thin stillage is concentrated, and this process condensate may be used as liquid for hydrolysis of further feedstock (e.g., grain) and/or as liquid in the fermentation medium.

[109] One embodiment of a larger overview of the process depicted in Figure 11 is shown in Figure 14. As shown in Figure 14, whole stillage that is recycled from the bottom of the beer column may be pretreated (e.g., hydrolyzed, for example, enzymatic hydrolysis) prior to combination with hydrolyzed grain.

[110] An alternative process configuration for bioproduct purification process is shown in Figure 12. In the configuration depicted in Figure 12, the vapor that is removed from the top of the beer stripping column is conducted to a distillation column (termed "acetone column" in Figure 12), without first condensing the vapor. A vapor that contains acetone, ethanol, and/or mixed solvents exits the top of the column and liquid that contains butanol exits the bottom of the column. In some embodiments, the vapor from the top of the distillation column may be condensed in one or more evaporators, optionally including a compressor (e.g., thermal or mechanical vapor recompression). Butanol purification, whole stillage recycle, and thin stillage processing may proceed, for example, as shown in Figure 10 and/or as described elsewhere herein.

[Ill] Figure 15 depicts an embodiment in which a fermentative ethanol production process is integrated with a process for production of one or more other bioproduct(s) of interest (e.g., butanol). As depicted in Figure 15, a feedstock (e.g., grain, such as corn) is processed and fermented by a first microorganism (e.g. , yeast) to produce a first bioproduct (e.g. , ethanol) in a first fermentation process, thereby producing a first fermentation medium that contains the first bioproduct and byproducts of the first fermentation process. Byproducts of the first fermentation process may include compounds or materials that are produced by the first microorganism and/or compounds or materials that are not metabolized by the first microorganism and/or spent microorganisms (e.g., including, but not limited to, acetic acid, lactic acid, glycerol, sugar molecules that are not metabolized in the first fermentation process, and/or spent yeast cells) are separated from the first bioproduct (e.g., ethanol) in the first fermentation medium. Processes for recovery of ethanol from fermentation medium are well known. For example, a process involving vacuum ethanol stripping and recovery of flash vapors from a flash tank and evaporators may be employed. Remaining components of the first fermentation medium (e.g., byproducts of the first fermentation) may be recovered and conducted to seed cultures of a second microorganism or to a second bioreactor for production of a second bioproduct of interest.

[112] Figure 1 schematically depicts an embodiment in which butanol and other solvents are recovered from solvent-containing fermentation broth ("beer"), e.g., from an ABE fermentation. Beer 101 is introduced into beer column 25, with withdrawal of whole stillage 102 from the beer column. The beer is heated in distillation column 25, and solvents are stripped out to produce a substantially solvent- free stillage 102 and a solvent- rich overhead vapor 103. Enriched solvent vapors 103 (e.g., about 20% (w/w) to about 55% (w/w) solvents) and thin stillage 130 are conducted to an evaporation system 30, and concentrated stillage 131 and evaporator condensate 104 are produced. Thin stillage 130 is evaporated to produce concentrated stillage 131, also called "syrup" herein. Evaporation system 30 may be of any suitable design or configuration, including but not limited to, falling film, forced recirculation, or plate and frame. A single effect or multiple effect system may be used, such as, for example, a system with 2, 3, or 4 effects. Condensed solvents 105 may be conducted to an acetone column 40, in which an acetone product 108 and a mixed solvent stream 109 are produced. Acetone column 40 is a distillation column that produces a purified acetone product overhead, a mixed solvent stream taken from a side-draw, and a bottoms product that contains primarily butanol and water. In some non- limiting embodiments, the acetone column is operated under vacuum, e.g., about 6 psia to about 15 psia pressure. In some embodiments, the acetone column is heated with a reboiler and the overhead vapors are condensed in a condenser. The condenser may have a vent stream and the vent stream may be part of a vacuum system if the column is operated below 1 bar-absolute pressure. In some embodiments, the reboiler may be heated with steam or may be heat-integrated with other parts of the process, such as, for example, the overhead vapors from the butanol column. Acetone column bottoms product 110 is conducted to decanter 50. A "decanter" herein is a tank or other container that allows liquid phases to separate. For example, the liquid in the decanter may separate into a butanol-rich "light phase" 111 and a water-rich "heavy phase" 112. Light phase 111 is conducted to butanol column 55 and heavy phase 112 may be recycled to beer column 25. Butanol column 55 is a distillation column that functions to strip water and other solvents from butanol, producing a purified butanol bottoms product 114 and an overhead vapor that may contain a mixture of butanol, water, and low levels of other solvents and contaminants. The vapor may be condensed or may be heat-integrated with other equipment such as, for example, a reboiler, e.g., a reboiler associated with the acetone column. Condensed overhead vapor 113 may be recycled to decanter 50.

[113] Another embodiment, in which two decanters, before and after the acetone column, are incorporated, is depicted schematically in Figure 2. Beer 201 is introduced into beer column 25, with withdrawal of whole stillage 202 from the beer column. Enriched solvent vapors 203 and thin stillage 230 are conducted to an evaporation system 30, and

concentrated stillage 231 and evaporator condensate 204 are produced. Thin stillage 230 is evaporated to produce concentrated stillage 231. Condensed solvents 205 may be conducted to a decanter 35. Light phase 206 is conducted to acetone column 40, in which an acetone product 208 and a mixed solvent stream 209 are produced. Heavy phase 207 may be recycled to beer column 25, e.g., mixed with feed 201 or used as reflux liquid. Acetone column bottoms product 210 is conducted to decanter 50. Light phase 211 is conducted to butanol column 55 and heavy phase 212 may be recycled to beer column 25. Butanol product 214 is recovered from butanol column 55. Condensed overhead vapor 213 may be recycled to decanter 50.

[114] Another embodiment, in which vapor from the beer column is introduced directly to the acetone column without first condensing solvents is depicted schematically in Figure 3. Beer 301 is introduced into beer column 25, with withdrawal of whole stillage 302 from the beer column. Enriched solvent vapors 303 are conducted to acetone column 40. Acetone- enriched vapor 305 and thin stillage 330 are conducted to evaporation system 30, and concentrated stillage 331 and evaporator condensate 304 are produced. Thin stillage 330 is evaporated to produce concentrated stillage 331. Acetone 308 is recovered from the condensed acetone-enriched liquid 306 exiting the evaporator system 30, and acetone reflux 307 is conducted to acetone column 40. Mixed solvent stream 309 is recovered via a side draw. Concentrated acetone vapor is condensed in evaporator system 30. A portion of the condensed acetone 306 is removed as acetone product 308. The remaining condensed acetone 307 is recycled as a reflux liquid into acetone column 40. Acetone column bottoms product 310 is conducted to decanter 50. Light phase 311 is conducted to butanol column 55 and heavy phase 312 may be recycled to beer column 25. Butanol product 314 is recovered from butanol column 55. Condensed overhead vapor 313 may be recycled to decanter 50.

[115] Figure 4 schematically depicts an embodiment in which butanol and other solvents are produced by fermentation of feedstock. Feedstock 401 is mixed 5 (e.g., with water) and optionally hydro lyzed (e.g., enzymatically hydro lyzed), for example, in one or more mixing and/or hydrolysis tanks, to produce a slurry 402 (e.g., mash), which is conducted to sterilization system 10, in which the slurry is heated to a temperature suitable to provide a sterilized, hot sugar stream 403 (e.g., hot sterilized mash). In some embodiments, heat is provided from recycled stillage 408. Heat may optionally be recovered 15 to provide a cooled, sterilized sugar stream 404. For example, heat recovery 15 may include one or more heat exchangers to cool the sterilized sugar composition and transfer the heat, for example, to beer that is produced in a downstream fermentation process. The heated beer may then be sent directly to beer column 25 or the heated beer may optionally be sent first to a system, such as a C0 ₂ flash tank, to remove C0 ₂ prior to distillation. After heat recovery 15, the sugar composition (e.g., mash) may be cooled to a temperature suitable for microbial fermentation, for example, in a mash cooler. Fermentation of the sterilized feedstock slurry is conducted 20, thereby producing bioproducts of interest, such as solvents (e.g., acetone, butanol, ethanol, crotyl alcohol). C0 ₂ is released through a vent system (not shown). The vent gas may include water, solvents, hydrogen, and/or organic acids.

Fermentation broth ("beer") is conducted to beer column 25. Optionally, the fermentation broth 405 is conducted through a heat recovery system 15 to heat the broth, producing heated broth 406, which is conducted to beer column 25. Bioproducts (e.g., solvents) may be recovered as described herein or as depicted in the drawings. In the embodiment depicted in Figure 4, beer (e.g., solvent-containing heated beer 406) is introduced into beer column 25, with withdrawal of whole stillage 408 from the beer column. Enriched solvent vapors 407 and thin stillage liquid (e.g., clarified whole stillage) 423 are conducted to an evaporation system 30, and concentrated thin stillage 424 and evaporator condensate (e.g., condensed solvents) 409 are produced. Thin stillage 423 is evaporated to produce evaporator condensate 425 and concentrated thin stillage 424. As depicted in Figure 4, condensed solvents 409 may be conducted to a decanter 35. Alternatively, condensed solvents 425 may be introduced directly into an acetone distillation column (not shown). In the embodiment depicted in Figure 4, light phase 411 is conducted to acetone column 40, in which an acetone product 412 and a mixed solvent stream 413 are produced. Heavy phase 410 may be recycled to beer column 25. Acetone column bottoms product 414 is conducted to decanter 50. Light phase 416 is conducted to butanol column 55 and heavy phase 415 may be recycled to beer column 25. Butanol product 418 is recovered from butanol column 55. Condensed overhead vapor 417 may be recycled to decanter 50. In the embodiment depicted in Figure 4, whole stillage 408 recovered from beer column 25 is conducted to flow splitter system 60, where it is recycled 440 and used to dilute sugar stream 402, while simultaneously heating it up for sterilization 10, and/or whole stillage may be sent to heat recovery system 65 via stream 420, where heat may be transferred evaporator condensate 425. Heat recovery system 65 may include, but is not limited to, a heat exchanger, e.g., plate-and-frame, shell-and-tube, spiral. Heated evaporator condensate 426 may be added to feedstock 401 as liquid for the slurry produced in 5. Cooled whole stillage 421 may be sent to separation system 70, which concentrates and removes suspended solids from the stillage, producing a "wet cake" 422 and "thin stillage" 423. Nonlimiting examples of separation systems include decanter centrifuges, presses, hydrocyclones, settling tanks, or other types of centrifuges. Thin stillage 423 is conducted to evaporator system 30, in which concentrated thin stillage 424 and evaporator condensate 425 are produced. Evaporator condensate 425 may be conducted to heat recovery system 65, where it is heated and used as liquid for preparation of feedstock slurry in mixing system 5.

[116] Another embodiment, in which recycled whole stillage is processed to provide additional soluble carbohydrate molecules, is depicted in Figure 5. Feedstock 501 is mixed 5 {e.g., with water) and optionally hydrolyzed {e.g., enzymatically hydrolyzed), for example, in one or more mixing and/or hydrolysis tanks, to produce a slurry 502 {e.g., mash), which is conducted to sterilization system 10, in which the slurry is heated to a temperature suitable to provide a sterilized, hot sugar stream 503 {e.g., hot sterilized mash). Heat may optionally be recovered 15 to provide a cooled, sterilized sugar stream 504. For example, heat recovery 15 may include one or more heat exchangers to cool the sterilized sugar composition and transfer the heat, for example, to beer that is produced in a downstream fermentation process. The heated beer 506 may then be sent directly to beer column 25 or the heated beer may optionally be sent first to a system, such as a C0 ₂ flash tank, to remove C0 ₂ prior to distillation. After heat recovery 15, the sugar composition (e.g. , mash) may be cooled to a temperature suitable for microbial fermentation, for example, in a mash cooler. Fermentation of the sterilized feedstock slurry is conducted 20, thereby producing bioproducts of interest, such as solvents (e.g., acetone, butanol, ethanol, crotyl alcohol). C0 ₂ is released through a vent system (not shown). The vent gas may include water, solvents, hydrogen, and/or organic acids. Fermentation broth ("beer") is conducted to beer column 25. Optionally, the fermentation broth 505 is conducted through a heat recovery system 15 to heat the broth, producing heated broth 506, which is conducted to beer column 25. Bioproducts (e.g., solvents) may be recovered as described herein or as depicted in the drawings. In the embodiment depicted in Figure 5, beer (e.g., solvent- containing heated beer 506) is introduced into beer column 25, with withdrawal of whole stillage 508 from the beer column. Enriched solvent vapors 507 and thin stillage liquid (e.g., clarified whole stillage) 523 are conducted to an evaporation system 30, and concentrated thin stillage 524 and evaporator condensate (e.g., condensed solvents) 525 are produced. Thin stillage 523 is evaporated to produce evaporator condensate 525 and concentrated thin stillage 524. As depicted in Figure 5, condensed solvents 509 may be conducted to a decanter 35. Alternatively, condensed solvents 509 may be introduced directly into an acetone distillation column (not shown). In the embodiment depicted in Figure 5, light phase 511 is conducted to acetone column 40, in which an acetone product 512 and a mixed solvent stream 513 are produced. Heavy phase 510 from decanter 35 may be recycled to beer column 25. Acetone column bottoms product 514 is conducted to decanter 50. Light phase 516 is conducted to butanol column 55 and heavy phase 515 may be recycled to beer column 25. Butanol product 518 is recovered from butanol column 55. Condensed overhead vapor 517 may be recycled to decanter 50. In the embodiment depicted in Figure 5, whole stillage 508 recovered from beer column 25 is conducted to flow splitter system 60, where it is conducted 540 to pretreatment and hydrolysis system 75 and/or sent to heat recovery system 65 via 520, where heat may be transferred to evaporator condensate 525. In 75, whole stillage may be processed to produce soluble sugar molecules, using a process such as, but not limited to, thermal, acid, and/or enzymatic hydrolysis. Pretreated whole stillage may be sterilized in sterilization system 10 and added to slurry 502 for microbial fermentation. Heated evaporator condensate 526 may be added to feedstock 501 as liquid for the slurry produced in 5. Cooled whole stillage 521,

conducted from flow splitting system 60 and through heat recovery system 65, may be sent to separation system 70, which concentrates and removes suspended solids from the stillage, producing a "wet cake" 522 and "thin stillage" 523. Thin stillage 523 is conducted to evaporator system 30, in which concentrated thin stillage 524 and evaporator condensate 525 are produced. Evaporator condensate 525 may be conducted to heat recovery system 65, where it is heated and used as liquid for preparation of feedstock slurry in mixing system 5.

[117] Figure 6 schematically depicts an embodiment in which ethanol is produced in a first fermentation that is upstream from a second fermentation in which butanol and other solvents are produced. In the embodiment depicted in Figure 6, feedstock 601 is mixed 80 (e.g., with water 620) and optionally hydrolyzed (e.g., enzymatically hydrolyzed), for example, in one or more mixing and/or hydrolysis tanks, to produce a slurry 602 (e.g., mash). Slurry 602 may be used for both ethanol fermentation 84 and fermentation to produce one or more bioproduct(s) (e.g., solvent(s) of interest 90, or alternatively, different pretreated feedstocks and/or slurries may be prepared from the same or different feedstock sources and/or feedstock portions for the two fermentation processes. Optionally, slurry 602 may be split in a flow splitting system 82 such that a portion of the slurry is conducted to ethanol fermentation 84 and a portion is conducted to bioproduct (e.g., solvent) fermentation 90. Alternatively, slurry 602 may be conducted solely to ethanol fermentation 84. Slurry 603 is fermented by an ethanol-producing microorganism to produce ethanol. Ethanol-containing fermentation broth ("ethanol fermentation beer") 605 is conducted to ethanol distillation system 86, in which ethanol 606 is stripped from the ethanol fermentation beer, rectified, and purified, e.g. , by molecular sieve dehydration, to produce ethanol product 605. Ethanol distillation whole stillage 607 is recovered as a bottoms product from ethanol distillation 86 and conducted to bioproduct (e.g. , solvent)

fermentation 90, where it is fermented, optionally in combination with slurried and/or hydrolyzed feedstock 604 by one or more bioproduct (e.g., solvent) producing

microorganism(s). In the embodiment depicted in Figure 6, butanol 611, acetone 612, and mixed solvents 613 are produced in fermentation 90 and recovered/purified 92 from the fermentation medium (solvent fermentation beer") 610, using recovery and purification processes described herein or known in the art. Whole stillage from the bioproduct (e.g. , solvent) fermentation 615 may be recovered and separated 94 into "wet cake" solids 616 and thin stillage 617. Thin stillage 617 may be evaporated 96 to produce concentrated stillage 618 and evaporator condensate 619. Optionally, whole stillage from the bioproduct (e.g., solvent) fermentation may be recovered and recycled 614 for inclusion in the fermentation medium 90 for further bioproduct (e.g., solvent) production. Optionally, evaporator condensate 619 may be recovered and recycled as liquid for pretreatment of further feedstock 80.

[118] Another embodiment, in which whole stillage from ethanol distillation is pretreated prior to introduction to downstream bioproduct (e.g., solvent) fermentation, is depicted in Figure 7. In the embodiment depicted in Figure 7, feedstock 701 is mixed 80 (e.g., with water 720) and optionally hydro lyzed (e.g., enzymatically hydro lyzed), for example, in one or more mixing and/or hydrolysis tanks, to produce a slurry 702 (e.g., mash). Slurry 702 may be used for both ethanol fermentation 84 and fermentation to produce one or more bioproduct(s) (e.g., solvent(s) of interest 90, or alternatively, different pretreated feedstocks and/or slurries may be prepared from the same or different feedstock sources and/or feedstock portions for the two fermentation processes. Optionally, slurry 702 may be split in a flow splitting system 82 such that a portion of the slurry is conducted to ethanol fermentation 84 and a portion is conducted to bioproduct (e.g., solvent) fermentation 90. Alternatively, slurry 702 may be conducted solely to ethanol fermentation 84. Slurry 703 is fermented by an ethanol-producing microorganism to produce ethanol. Ethanol-containing fermentation broth ("ethanol fermentation beer") 705 is conducted to ethanol distillation system 86, in which ethanol 706 is stripped from the ethanol fermentation beer, rectified, and purified, e.g., by molecular sieve dehydration, to produce ethanol product 705. Ethanol distillation whole stillage 707 is recovered as a bottoms product from ethanol distillation 86 and conducted to pretreatment system 88, in which soluble sugar molecules are produced from the whole stillage, for example, by thermal, acid, and/or enzymatic hydrolysis.

Pretreated whole stillage 708 is fed to bioproduct (e.g., solvent) fermentation 90, where it is fermented, optionally in combination with slurried and/or hydrolyzed feedstock 704 by one or more bioproduct (e.g., solvent) producing microorganism(s). In the embodiment depicted in Figure 7, butanol 711, acetone 712, and mixed solvents 713 are produced in fermentation 90 and recovered/purified 92 from the fermentation medium (solvent fermentation beer) 710, using recovery and purification processes described herein or known in the art. Whole stillage from the bioproduct (e.g., solvent) fermentation 715 may be recovered and separated 94 into "wet cake" solids 716 and thin stillage 717. Thin stillage 717 may be evaporated 96 to produce concentrated stillage 718 and evaporator condensate 719. Optionally, whole stillage from the bioproduct (e.g., solvent) fermentation may be recovered and recycled 714 for inclusion in the fermentation medium 90 for further bioproduct (e.g., solvent) production. Optionally, evaporator condensate 719 may be recovered and recycled as liquid for pretreatment of further feedstock 80.

[119] Figure 8 schematically depicts an embodiment of an acetone distillation column. Feed 801 into acetone distillation column 40 contains acetone, water, and other solvents (e.g., butanol, ethanol, and/or crotyl alcohol), along with other organic and inorganic impurities. The column contains a reboiler. Heat 802 is supplied to the reboiler, for example, from steam or from a process stream such as, for example, heat recovered from butanol column overhead vapor. Acetone 804 is recovered from the top of the column, mixed solvents 810 are recovered in a side draw, and the bottoms product 811 includes primarily butanol (and/or crotyl alcohol) and water, and may also include some impurities. Impurities and some acetone may be vented through vent 803. For example, in some embodiments less than about 1%, less than about 5%, or less than about 10% of the vapor produced at the top of the column is vented through vent 803. The vent gas may be routed directly to a scrubber if the acetone distillation column is operated at atmospheric pressure, or in the case of vacuum operation (less than 15 psia pressure), it may be routed to a vacuum system (e.g., vacuum pump), which discharges the vapor to the scrubber.

[120] Another embodiment, in which the side draw is routed through a solvent flash column, is depicted in Figure 9. Feed 901 is conducted into acetone distillation column 40 Heat 902 is supplied to the reboiler, for example, from steam or from a process stream such as, for example, heat recovered from butanol column overhead vapor. Acetone 904 is recovered from the top of the column, and side draw 907, containing mixed solvents, is conducted to solvent flash column 45, a distillation column that can be, for example, a packed or trayed column. The solvent flash column recovers acetone from the mixed solvent draw. Solvent flash column 45 may be heated, for example, directly with steam 909 or indirectly with a reboiler. The heat strips acetone from the side product and improves acetone recovery in the overall acetone distillation system. Vapor 908 may be recycled from the top of flash solvent column 45 to the acetone distillation column 40. Vapor 908 contains primarily acetone, and may also contain water, ethanol, and/or other impurities. Mixed solvents 910 are recovered from the bottom of solvent flash column 45.

Bottoms product 911 includes primarily butanol (and/or crotyl alcohol) and water, and may also include some impurities. Acetone and some impurities are vented through vent 903. The vent gas may be routed to a scrubber, or in the case of vacuum operation, it may be routed to a vacuum system. [121] Although the foregoing invention has been described in some detail by way of illustration and examples for purposes of clarity of understanding, it will be apparent to those skilled in the art that certain changes and modifications may be practiced without departing from the spirit and scope of the invention, which is delineated in the appended claims. Therefore, the description should not be construed as limiting the scope of the invention.

[122] All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entireties for all purposes and to the same extent as if each individual publication, patent, or patent application were specifically and individually indicated to be so incorporated by reference.