The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids.

Microbiology
Sivagami Sundaram ChavadiLuis E N Quadri

Abstract

Phenolic glycolipids (PGLs) are non-covalently bound components of the outer membrane of many clinically relevant mycobacterial pathogens, and play important roles in pathogen biology. We report a mutational analysis that conclusively demonstrates that the conserved acyltransferase-encoding gene papA5 is essential for PGL production. In addition, we provide an in vitro acyltransferase activity analysis that establishes proof of principle for the competency of PapA5 to utilize diol-containing polyketide compounds of mycobacterial origin as acyl-acceptor substrates. Overall, the results reported herein are in line with a model in which PapA5 catalyses the acylation of diol-containing polyketides to form PGLs. These studies advance our understanding of the biosynthesis of an important group of mycobacterial glycolipids and suggest that PapA5 might be an attractive target for exploring the development of antivirulence drugs.

References

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Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kenolisa C OnwuemeLuis E N Quadri
May 5, 2004·The Journal of Biological Chemistry·John BuglinoChristopher D Lima
Aug 24, 2005·Progress in Lipid Research·Kenolisa C OnwuemeLuis E N Quadri
Jan 13, 2006·Nature Chemical Biology·Julian A FerrerasLuis E N Quadri
Sep 28, 2007·Infectious Disorders Drug Targets·Luis E N Quadri
Jun 20, 2008·Proteomics·Maria Angela M MarquesMaria Cristina V Pessolani
Jul 22, 2008·Drug Metabolism Reviews·Kirsty J McLean, Andrew W Munro
Jul 23, 2009·The Journal of Infectious Diseases·Jeffrey P MurryEric J Rubin
May 20, 2011·The Journal of Biological Chemistry·Sivagami Sundaram ChavadiLuis E N Quadri
Aug 30, 2011·Journal of Bacteriology·Sivagami Sundaram ChavadiLuis E N Quadri

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Citations

Dec 4, 2014·Chemistry & Biology·Sabine GavaldaAnnaïk Quémard
Mar 15, 2014·Critical Reviews in Biochemistry and Molecular Biology·Luis E N Quadri
Jul 12, 2017·ACS Chemical Biology·Danielle D BarnesEoin M Scanlan
May 24, 2013·Microbiology and Molecular Biology Reviews : MMBR·Annika Röttig, Alexander Steinbüchel
May 18, 2016·Journal of Bacteriology·Endang PurwantiniBiswarup Mukhopadhyay
Jan 7, 2015·Journal of Bacteriology·Olivia VergnolleLuis E N Quadri

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