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

Sivagami Sundaram Chavadi, Kenolisa C. Onwueme, Uthamaphani R. Edupuganti, Jeff Jerome, Delphi Chatterjee, Clifford E. Soll, Luis E N Quadri

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1379-1387
Number of pages9
JournalMicrobiology
Volume158
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

Fingerprint

Acyltransferases
Glycolipids
Cell Wall
Polyketides
Acylation
Membranes
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • Microbiology

Cite this

Chavadi, S. S., Onwueme, K. C., Edupuganti, U. R., Jerome, J., Chatterjee, D., Soll, C. E., & Quadri, L. E. N. (2012). The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids. Microbiology, 158(5), 1379-1387. https://doi.org/10.1099/mic.0.057869-0

The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids. / Chavadi, Sivagami Sundaram; Onwueme, Kenolisa C.; Edupuganti, Uthamaphani R.; Jerome, Jeff; Chatterjee, Delphi; Soll, Clifford E.; Quadri, Luis E N.

In: Microbiology, Vol. 158, No. 5, 05.2012, p. 1379-1387.

Research output: Contribution to journalArticle

Chavadi, SS, Onwueme, KC, Edupuganti, UR, Jerome, J, Chatterjee, D, Soll, CE & Quadri, LEN 2012, 'The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids', Microbiology, vol. 158, no. 5, pp. 1379-1387. https://doi.org/10.1099/mic.0.057869-0
Chavadi SS, Onwueme KC, Edupuganti UR, Jerome J, Chatterjee D, Soll CE et al. The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids. Microbiology. 2012 May;158(5):1379-1387. https://doi.org/10.1099/mic.0.057869-0
Chavadi, Sivagami Sundaram ; Onwueme, Kenolisa C. ; Edupuganti, Uthamaphani R. ; Jerome, Jeff ; Chatterjee, Delphi ; Soll, Clifford E. ; Quadri, Luis E N. / The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids. In: Microbiology. 2012 ; Vol. 158, No. 5. pp. 1379-1387.
@article{25f8c67a0850440faff3f15d3287ac6b,
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.",
author = "Chavadi, {Sivagami Sundaram} and Onwueme, {Kenolisa C.} and Edupuganti, {Uthamaphani R.} and Jeff Jerome and Delphi Chatterjee and Soll, {Clifford E.} and Quadri, {Luis E N}",
year = "2012",
month = "5",
doi = "10.1099/mic.0.057869-0",
language = "English (US)",
volume = "158",
pages = "1379--1387",
journal = "Microbiology (United Kingdom)",
issn = "1350-0872",
publisher = "Society for General Microbiology",
number = "5",

}

TY - JOUR

T1 - The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids

AU - Chavadi, Sivagami Sundaram

AU - Onwueme, Kenolisa C.

AU - Edupuganti, Uthamaphani R.

AU - Jerome, Jeff

AU - Chatterjee, Delphi

AU - Soll, Clifford E.

AU - Quadri, Luis E N

PY - 2012/5

Y1 - 2012/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84860528767&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860528767&partnerID=8YFLogxK

U2 - 10.1099/mic.0.057869-0

DO - 10.1099/mic.0.057869-0

M3 - Article

VL - 158

SP - 1379

EP - 1387

JO - Microbiology (United Kingdom)

JF - Microbiology (United Kingdom)

SN - 1350-0872

IS - 5

ER -