title: The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids.
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.
authors.affiliation: Department of Biology, Brooklyn College - City University of New York, Brooklyn, NY 11210, USA.
authors.forename: Sivagami Sundaram
authors.initials: SS
authors.lastname: Chavadi
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, NY 10021, USA.
authors.forename: Kenolisa C
authors.initials: KC
authors.lastname: Onwueme
authors.affiliation: Department of Biology, Brooklyn College - City University of New York, Brooklyn, NY 11210, USA.
authors.forename: Uthamaphani R
authors.initials: UR
authors.lastname: Edupuganti
authors.affiliation: Department of Biology, Brooklyn College - City University of New York, Brooklyn, NY 11210, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Jerome
authors.affiliation: Microbiology, Immunology and Pathology Department, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Delphi
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Chemistry Department, Hunter College - City University of New York, NY 10065, USA.
authors.forename: Clifford E
authors.initials: CE
authors.lastname: Soll
authors.affiliation: Department of Biology, Brooklyn College - City University of New York, Brooklyn, NY 11210, USA.
authors.forename: Luis E N
authors.initials: LEN
authors.lastname: Quadri
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics; D006017:Glycolipids / Q000096:biosynthesis*; D054878:Lipoylation; D009154:Mutation; D019910:Mycobacterium marinum / Q000201:enzymology* / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D006017:Glycolipids; D000217:Acyltransferases; C487811:PapA5 protein, Mycobacterium tuberculosis