Search anything and hit enter
  • Teams
  • Members
  • Projects
  • Events
  • Calls
  • Jobs
  • publications
  • Software
  • Tools
  • Network
  • Equipment

A little guide for advanced search:

  • Tip 1. You can use quotes "" to search for an exact expression.
    Example: "cell division"
  • Tip 2. You can use + symbol to restrict results containing all words.
    Example: +cell +stem
  • Tip 3. You can use + and - symbols to force inclusion or exclusion of specific words.
    Example: +cell -stem
e.g. searching for members in projects tagged cancer
Search for
Count
IN
OUT
Content 1
  • member
  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Clinical Research Nurse
  • Clinician Researcher
  • Department Manager
  • Dual-education Student
  • Full Professor
  • Honorary Professor
  • Lab assistant
  • Master Student
  • Non-permanent Researcher
  • Nursing Staff
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Prize
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
Content 2
  • member
  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Clinical Research Nurse
  • Clinician Researcher
  • Department Manager
  • Dual-education Student
  • Full Professor
  • Honorary Professor
  • Lab assistant
  • Master Student
  • Non-permanent Researcher
  • Nursing Staff
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Prize
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
Search
Go back
Scroll to top
Share
© Clifton E. Barry III, Ph.D., NIAID, NIH.
Colorized scanning electron micrograph of Mycobacterium tuberculosis
Publication : Proceedings of the National Academy of Sciences of the United States of America

Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 21 Jan 2004

Stinear TP, Mve-Obiang A, Small PL, Frigui W, Pryor MJ, Brosch R, Jenkin GA, Johnson PD, Davies JK, Lee RE, Adusumilli S, Garnier T, Haydock SF, Leadlay PF, Cole ST

Link to Pubmed [PMID] – 14736915

Proc. Natl. Acad. Sci. U.S.A. 2004 Feb;101(5):1345-9

Mycobacterium ulcerans (MU), an emerging human pathogen harbored by aquatic insects, is the causative agent of Buruli ulcer, a devastating skin disease rife throughout Central and West Africa. Mycolactone, an unusual macrolide with cytotoxic and immunosuppressive properties, is responsible for the massive s.c. tissue destruction seen in Buruli ulcer. Here, we show that MU contains a 174-kb plasmid, pMUM001, bearing a cluster of genes encoding giant polyketide synthases (PKSs), and polyketide-modifying enzymes, and demonstrate that these are necessary and sufficient for mycolactone synthesis. This is a previously uncharacterized example of plasmid-mediated virulence in a Mycobacterium, and the emergence of MU as a pathogen most likely reflects the acquisition of pMUM001 by horizontal transfer. The 12-membered core of mycolactone is produced by two giant, modular PKSs, MLSA1 (1.8 MDa) and MLSA2 (0.26 MDa), whereas its side chain is synthesized by MLSB (1.2 MDa), a third modular PKS highly related to MLSA1. There is an extreme level of sequence identity within the different domains of the MLS cluster (>97% amino acid identity), so much so that the 16 ketosynthase domains seem functionally identical. This is a finding of significant consequence for our understanding of polyketide biochemistry. Such detailed knowledge of mycolactone will further the investigation of its mode of action and the development of urgently needed therapeutic strategies to combat Buruli ulcer.