Type I modular polyketide synthase

GENE NAME 

Type I modular polyketide synthase

ORGANISM 

Mycobacterium ulcerans (strain Agy99)

GENE NAME 


mlsA1

GENE ID 

2846548

TDR TARGET ID 

954920

PROTEIN LENGTH 

16,990

FUNCTION 

Required for the Synthesis of the polyketide toxin mycolactone.                        
Enhances the virulence of the Mycobacterium ulcerans.
 
Blocks exocytosis by blood platelets 
and mast cells,
Impaires wound healing processes

Has immunosuppresive properties
Inhibits phagocytic activities of white 
blood cells and kills neutrophils that 
are dispatched to infected cells.

UNIPROT ID 

Q6MZA4

KEGG PATHWAY 

mul:MUP040c

GO - MOLECULAR FUNCTION 

GO:0004315

GO:0016491

GO:0031177

GO - BIOLOGICAL PROCESS 

GO:0006633

LINK TO PUBMED 

https://pubmed.ncbi.nlm.nih.gov/15758215/

https://pubmed.ncbi.nlm.nih.gov/14736915/

https://pubmed.ncbi.nlm.nih.gov/30934618/

https://pubmed.ncbi.nlm.nih.gov/24699819/

REFERENCE 

Stinear, T. P., Pryor, M. J., Porter, J. L., & Cole, S. T. (2005). Functional analysis and annotation of the virulence plasmid pMUM001 from Mycobacterium ulcerans. Microbiology, 151(3), 683-692. https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.27674-0


Stinear, T. P., Mve-Obiang, A., Small, P. L. C., Frigui, W., Pryor, M. J., Brosch, R., Jenkin, G. A., Johnson, P. D. R., Davies, J. K., Lee, R. E., Adusumilli, S., Garnier, T., Haydock, S. F., Leadlay, P. F., & Cole, S. T. (2004). Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans. Proceedings of the National Academy of Sciences, 101(5), 1345-1349. https://doi.org/10.1099/mic.0.27674-0

Kwofie, S. K., Dankwa, B., Enninful, K. S., Adobor, C., Broni, E., Ntiamoah, A., & Wilson, M. D. (2019). Molecular Docking and Dynamics Simulation Studies Predict Munc18b as a Target of Mycolactone: A Plausible Mechanism for Granule Exocytosis Impairment in Buruli Ulcer Pathogenesis. Toxins, 11(3). https://doi.org/10.3390/TOXINS11030181

Hall, B. S., Hill, K., McKenna, M., Ogbechi, J., High, S., Willis, A. E., & Simmonds, R. E. (2014). The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER. PLoS Pathogens, 10(4). https://doi.org/10.1371/JOURNAL.PPAT.1004061