Title:
THE MYCOLACTONE LOCUS : AN ASSEMBLY LINE FOR PRODUCING NOVEL POLYKETIDES, WITH THERAPEUTIC AND PROPHYLATIC USES
Document Type and Number:
WIPO Patent Application WO2005047509
Kind Code:
A3
Abstract:
The present invention relates to Mycobacterium ulceran virulence plasmid, pMUM001 and particularly to a cluster of genes carried by this plasmid that encode polyketide synthases (PKSs) and polyketide-modifying enzymes necessary and sufficient for mycolactone biosynthesis. More particularly this invention is directed to novel purified or isolated polypeptides, the polynucleotides encoding such polypeptides, processes for production of such polypeptides, antibodies generated against these polypeptides, the use of such polynucleotides and polypeptides in diagnostic methods, kits, vaccines, therapy and for the production of mycolactone derivatives or novel polyketides by combinatorial synthesis.
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Inventors:
STINEAR TIMOTHY PAUL (FR)
COLE STEWART THOMAS (FR)
LEADLAY PETER FRANCIS (GB)
SMALL PAMELA LONG CLAUS (US)
DAVIES JOHN KEITH (AU)
JENKIN GRANT ADAM (AU)
HAYDOCK STEPHEN FREDERICK (GB)
JOHNSON PAUL (AU)
COLE STEWART THOMAS (FR)
LEADLAY PETER FRANCIS (GB)
SMALL PAMELA LONG CLAUS (US)
DAVIES JOHN KEITH (AU)
JENKIN GRANT ADAM (AU)
HAYDOCK STEPHEN FREDERICK (GB)
JOHNSON PAUL (AU)
Application Number:
PCT/IB2004/003999
Publication Date:
July 20, 2006
Filing Date:
November 15, 2004
Export Citation:
Assignee:
UNIV TENNESSEE (US)
UNIV MONASH (AU)
AUSTIN UNIVERSITY (AU)
BIOTICA TECHNOLOGY (GB)
STINEAR TIMOTHY PAUL (FR)
COLE STEWART THOMAS (FR)
LEADLAY PETER FRANCIS (GB)
SMALL PAMELA LONG CLAUS (US)
DAVIES JOHN KEITH (AU)
JENKIN GRANT ADAM (AU)
HAYDOCK STEPHEN FREDERICK (GB)
JOHNSON PAUL (AU)
UNIV MONASH (AU)
AUSTIN UNIVERSITY (AU)
BIOTICA TECHNOLOGY (GB)
STINEAR TIMOTHY PAUL (FR)
COLE STEWART THOMAS (FR)
LEADLAY PETER FRANCIS (GB)
SMALL PAMELA LONG CLAUS (US)
DAVIES JOHN KEITH (AU)
JENKIN GRANT ADAM (AU)
HAYDOCK STEPHEN FREDERICK (GB)
JOHNSON PAUL (AU)
International Classes:
C12N15/52; C12N9/00; C12P17/08; C12Q1/68; G01N33/50; C12R1/32
Domestic Patent References:
| WO2001019993A2 | 2001-03-22 | |||
| WO2000075126A1 | 2000-12-14 | |||
| WO2002012533A2 | 2002-02-14 |
Other References:
DATABASE EMBL [online] EBI; 1 November 2003 (2003-11-01), "Mycobacterium ulcerans clone B type I polyketide synthase extender module gene, partial cds.", XP002328658, retrieved from EBI accession no. EM_PRO:AY289594 Database accession no. AY289594
DATABASE EMBL [online] EBI; 1 November 2003 (2003-11-01), "Mycobacterium ulcerans FabH-like protein and type I polyketide synthase loading module genes, partial cds.", XP002328659, retrieved from EBI accession no. EM_PRO:AY289593 Database accession no. AY289593
DATABASE EMBL [online] EBI; 10 June 2003 (2003-06-10), "Mycobacterium bovis subsp. bovis AF2122/97 complete genome; segment 7/14", XP002328660, retrieved from EBI accession no. EM_PRO:BX248340 Database accession no. BX248340
DATABASE EMBL [online] 3 April 2003 (2003-04-03), "Streptomyces murayamaensis putative arylamine N-acetyltransferase, putative hydrolase, putative transmembrane efflux protein, putative transcriptional regulator, putative ribonuclease HII, putative ATP-dependent DNA helicase, putative bifunctional enzyme deaminase/reductase genes, complete cds; kina", XP002328661, retrieved from EBI accession no. EM_PRO:AY228175 Database accession no. AY228175
VAN DER WERF T S ET AL: "Mycolactones and Mycobacterium ulcerans disease", LANCET THE, vol. 362, no. 9389, 27 September 2003 (2003-09-27), pages 1062 - 1064, XP004778424, ISSN: 0140-6736
WORLD HEALTH ORGANIZATION: "REPORT: 3rd WHO Advisory Group Meeting on Buruli ulcer", INTERNET ARTICLE, 1 March 2000 (2000-03-01) - 3 March 2000 (2000-03-03), XP002328650, Retrieved from the Internet [retrieved on 20050512]
STINEAR T P ET AL: "Comparative genetic analysis of Mycobacterium ulcerans and Mycobacterium marinum reveals evidence of recent divergence.", JOURNAL OF BACTERIOLOGY, vol. 182, no. 22, November 2000 (2000-11-01), pages 6322 - 6330, XP002328651
ALFORD T D ET AL: "Identification of a putative mycolactone negative mutant", ABSTRACTS OF THE GENERAL MEETING OF THE AMERICAN SOCIETY FOR MICROBIOLOGY, vol. 102, 2002, & 102ND GENERAL MEETING OF THE AMERICAN SOCIETY FOR MICROBIOLOGY; SALT LAKE CITY, UT, USA; MAY 19-23, 2002, pages 481, XP008047081, ISSN: 1060-2011
ALFORD T D ET AL: "FurA: A putative regulator of mycolactone production.", ABSTRACTS OF THE GENERAL MEETING OF THE AMERICAN SOCIETY FOR MICROBIOLOGY, vol. 103, 2003, & 103RD AMERICAN SOCIETY FOR MICROBIOLOGY GENERAL MEETING; WASHINGTON, DC, USA; MAY 18-22, 2003, pages A - 122 URL, XP008047080, ISSN: 1060-2011
MVE-OBIANG A ET AL: "Heterogeneity of mycolactones produced by clinical isolates of Mycobacterium ulcerans: implications for virulence.", INFECTION AND IMMUNITY, vol. 71, no. 2, February 2003 (2003-02-01), pages 774 - 783, XP002328652, ISSN: 0019-9567
GEORGE K M ET AL: "Mycolactone. A Polyketide Toxin from Mycobacterium Ulcerans Required for Virulence", SCIENCE, vol. 283, no. 5403, 5 February 1999 (1999-02-05), pages 854 - 857, XP002148650, ISSN: 0036-8075
CADAPAN L D ET AL: "Suspension cultivation of Mycobacterium ulcerans for the production of mycolactones", FEMS MICROBIOLOGY LETTERS, vol. 205, no. 2, 2001, pages 385 - 389, XP002201043, ISSN: 0378-1097
STINEAR T ET AL: "A simple PCR method for rapid genotype analysis of Mycobacterium ulcerans .", JOURNAL OF CLINICAL MICROBIOLOGY, vol. 38, no. 4, April 2000 (2000-04-01), pages 1482 - 1487, XP002328653
JENKIN G A ET AL: "Subtractive hybridization reveals a type I polyketide synthase locus specific to Mycobacterium ulcerans.", JOURNAL OF BACTERIOLOGY, vol. 185, no. 23, December 2003 (2003-12-01), pages 6870 - 6882, XP002328654, ISSN: 0021-9193
STINEAR T P ET AL: "Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 101, no. 5, February 2004 (2004-02-01), pages 1345 - 1349, XP002328655, ISSN: 0027-8424
STINEAR T P ET AL: "Functional analysis and annotation of the virulence plasmid pMUM001 from Mycobacterium ulcerans.", MICROBIOLOGY, vol. 151, no. Pt 3, March 2005 (2005-03-01), pages 683 - 692, XP002328656, ISSN: 1350-0872
TOWNSEND C A: "Buruli toxin genes decoded.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 101, no. 5, 3 February 2004 (2004-02-03), pages 1116 - 1117, XP002328657, ISSN: 0027-8424
DATABASE EMBL [online] EBI; 1 November 2003 (2003-11-01), "Mycobacterium ulcerans FabH-like protein and type I polyketide synthase loading module genes, partial cds.", XP002328659, retrieved from EBI accession no. EM_PRO:AY289593 Database accession no. AY289593
DATABASE EMBL [online] EBI; 10 June 2003 (2003-06-10), "Mycobacterium bovis subsp. bovis AF2122/97 complete genome; segment 7/14", XP002328660, retrieved from EBI accession no. EM_PRO:BX248340 Database accession no. BX248340
DATABASE EMBL [online] 3 April 2003 (2003-04-03), "Streptomyces murayamaensis putative arylamine N-acetyltransferase, putative hydrolase, putative transmembrane efflux protein, putative transcriptional regulator, putative ribonuclease HII, putative ATP-dependent DNA helicase, putative bifunctional enzyme deaminase/reductase genes, complete cds; kina", XP002328661, retrieved from EBI accession no. EM_PRO:AY228175 Database accession no. AY228175
VAN DER WERF T S ET AL: "Mycolactones and Mycobacterium ulcerans disease", LANCET THE, vol. 362, no. 9389, 27 September 2003 (2003-09-27), pages 1062 - 1064, XP004778424, ISSN: 0140-6736
WORLD HEALTH ORGANIZATION: "REPORT: 3rd WHO Advisory Group Meeting on Buruli ulcer", INTERNET ARTICLE, 1 March 2000 (2000-03-01) - 3 March 2000 (2000-03-03), XP002328650, Retrieved from the Internet
STINEAR T P ET AL: "Comparative genetic analysis of Mycobacterium ulcerans and Mycobacterium marinum reveals evidence of recent divergence.", JOURNAL OF BACTERIOLOGY, vol. 182, no. 22, November 2000 (2000-11-01), pages 6322 - 6330, XP002328651
ALFORD T D ET AL: "Identification of a putative mycolactone negative mutant", ABSTRACTS OF THE GENERAL MEETING OF THE AMERICAN SOCIETY FOR MICROBIOLOGY, vol. 102, 2002, & 102ND GENERAL MEETING OF THE AMERICAN SOCIETY FOR MICROBIOLOGY; SALT LAKE CITY, UT, USA; MAY 19-23, 2002, pages 481, XP008047081, ISSN: 1060-2011
ALFORD T D ET AL: "FurA: A putative regulator of mycolactone production.", ABSTRACTS OF THE GENERAL MEETING OF THE AMERICAN SOCIETY FOR MICROBIOLOGY, vol. 103, 2003, & 103RD AMERICAN SOCIETY FOR MICROBIOLOGY GENERAL MEETING; WASHINGTON, DC, USA; MAY 18-22, 2003, pages A - 122 URL, XP008047080, ISSN: 1060-2011
MVE-OBIANG A ET AL: "Heterogeneity of mycolactones produced by clinical isolates of Mycobacterium ulcerans: implications for virulence.", INFECTION AND IMMUNITY, vol. 71, no. 2, February 2003 (2003-02-01), pages 774 - 783, XP002328652, ISSN: 0019-9567
GEORGE K M ET AL: "Mycolactone. A Polyketide Toxin from Mycobacterium Ulcerans Required for Virulence", SCIENCE, vol. 283, no. 5403, 5 February 1999 (1999-02-05), pages 854 - 857, XP002148650, ISSN: 0036-8075
CADAPAN L D ET AL: "Suspension cultivation of Mycobacterium ulcerans for the production of mycolactones", FEMS MICROBIOLOGY LETTERS, vol. 205, no. 2, 2001, pages 385 - 389, XP002201043, ISSN: 0378-1097
STINEAR T ET AL: "A simple PCR method for rapid genotype analysis of Mycobacterium ulcerans .", JOURNAL OF CLINICAL MICROBIOLOGY, vol. 38, no. 4, April 2000 (2000-04-01), pages 1482 - 1487, XP002328653
JENKIN G A ET AL: "Subtractive hybridization reveals a type I polyketide synthase locus specific to Mycobacterium ulcerans.", JOURNAL OF BACTERIOLOGY, vol. 185, no. 23, December 2003 (2003-12-01), pages 6870 - 6882, XP002328654, ISSN: 0021-9193
STINEAR T P ET AL: "Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 101, no. 5, February 2004 (2004-02-01), pages 1345 - 1349, XP002328655, ISSN: 0027-8424
STINEAR T P ET AL: "Functional analysis and annotation of the virulence plasmid pMUM001 from Mycobacterium ulcerans.", MICROBIOLOGY, vol. 151, no. Pt 3, March 2005 (2005-03-01), pages 683 - 692, XP002328656, ISSN: 1350-0872
TOWNSEND C A: "Buruli toxin genes decoded.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 101, no. 5, 3 February 2004 (2004-02-03), pages 1116 - 1117, XP002328657, ISSN: 0027-8424
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