Diacyltransferase Activity and Chain Length Specificity of Mycobacterium tuberculosis PapA5 in the Synthesis of Alkyl β-Diol Lipids.

@article{Touchette2015DiacyltransferaseAA,
  title={Diacyltransferase Activity and Chain Length Specificity of Mycobacterium tuberculosis PapA5 in the Synthesis of Alkyl $\beta$-Diol Lipids.},
  author={Megan H Touchette and Gopal R. Bommineni and Richard J Delle Bovi and John E Gadbery and Carrie D. Nicora and Anil K. Shukla and Jennifer E. Kyle and Thomas O. Metz and Dwight Martin and Nicole S. Sampson and William T. Miller and Peter J. Tonge and Jessica C. Seeliger},
  journal={Biochemistry},
  year={2015},
  volume={54 35},
  pages={
          5457-68
        }
}
Although they are classified as Gram-positive bacteria, Corynebacterineae possess an asymmetric outer membrane that imparts structural and thereby physiological similarity to more distantly related Gram-negative bacteria. Like lipopolysaccharide in Gram-negative bacteria, lipids in the outer membrane of Corynebacterineae have been associated with the virulence of pathogenic species such as Mycobacterium tuberculosis (Mtb). For example, Mtb strains that lack long, branched-chain alkyl esters… 

Figures and Tables from this paper

Modification of PapA5 acyltransferase substrate selectivity for optimization of short-chain alcohol-derived multimethyl-branched ester production in Escherichia coli.
TLDR
Two alternative pathways for synthetizing ethanol were engineered into the MBE producer microorganism, allowing de novo production of ethanol-derived MBE at levels comparable with those obtained by the external supply of this alcohol.
A novel mutation alters the stability of PapA2 resulting in the complete abrogation of sulfolipids in clinical mycobacterial strains
TLDR
The present study demonstrates the importance of a critical structural residue in the papA2 protein of Mtb and helps establish a link between observed genomic alteration and its molecular consequence in the successful human pathogen Mtb.
A novel mutation alters the stability of PapA2 resulting in the complete abrogation of sulfolipids in clinical mycobacterial strains
TLDR
This study demonstrates the importance of a critical structural residue in the papA2 protein of Mtb and helps establish a link between observed genomic alteration and its molecular consequence in the successful human pathogen Mtb.
Epigenetic Phosphorylation Control of Mycobacterium tuberculosis Infection and Persistence.
TLDR
The role of M. tuberculosis serine/threonine protein kinases in sensing the host environment to coordinate the bacilli's physiology, including growth, cell wall components, and central metabolism, to establish a persistent infection is focused on.

References

SHOWING 1-10 OF 74 REFERENCES
PapA3 Is an Acyltransferase Required for Polyacyltrehalose Biosynthesis in Mycobacterium tuberculosis*S⃞
TLDR
It is determined that the PAT biosynthetic machinery has no cross-talk with that for sulfolipid-1 despite their related structures, demonstrating that PapA3 is essential for the biosynthesis of this glycolipid in vivo.
Two polyketide-synthase-associated acyltransferases are required for sulfolipid biosynthesis in Mycobacterium tuberculosis.
TLDR
It was demonstrated that another open reading frame, Rv3820c (papA2), located 5.8 kb downstream of papA1 is also an acyltransferase gene involved in SL-I biosynthesis: deletion of papC2 abolished SL- I production, demonstrating its role in mycobacterial sulfolipid biosynthesis.
Biosynthesis of Cell Envelope-Associated Phenolic Glycolipids in Mycobacterium marinum
TLDR
The partially overlapping PGL and PDIM biosynthetic pathways provide the first example of two distinct, pathway-dedicated acyl-AMP ligases loading the same type I polyketide synthase system with two alternate starter units to produce two structurally different families of metabolites.
PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor Sulfolipid-1
TLDR
It is demonstrated that PapA2 and PapA1 are responsible for the sequential acylation of T2S to form SL1278 and are essential for SL-1 biosynthesis.
Crystal Structure of PapA5, a Phthiocerol Dimycocerosyl Transferase from Mycobacterium tuberculosis*
TLDR
PapA5 represents the first structure solved for a protein involved in polyketide synthesis in Mycobacteria and shares unexpected similarity to structures of chloramphenicol acetyl transferase, dihydrolipoyl transacetylase, carnitine acetyltransferase, and VibH, a non-ribosomal peptide synthesis condensation enzyme.
Mycobacterial polyketide-associated proteins are acyltransferases: proof of principle with Mycobacterium tuberculosis PapA5.
TLDR
It is proposed that PapA5 catalyzes diesterification of phthiocerol and phthiodiolone with mycocerosate and permit inferences regarding roles of other Paps in the synthesis of complex lipids, including the antibiotic rifamycin.
Biosynthesis of mycobacterial lipids by polyketide synthases and beyond
  • L. Quadri
  • Biology, Chemistry
    Critical reviews in biochemistry and molecular biology
  • 2014
TLDR
A synopsis of the most relevant studies in the field and an overview of the current understanding of the involvement of PKSs and several other polyketide production pathway-associated proteins in critical biosynthetic pathways of M. tuberculosis and other mycobacteria are provided.
Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Evidence that this lipid is involved in the cell wall permeability barrier.
TLDR
Insertional mutants unable to synthesize or translocate DIMs exhibit higher cell wall permeability and are more sensitive to detergent than the wild type strain, indicating for the first time that, in addition to being important virulence factors, extractable lipids of M. tuberculosis play a role in the cell envelope architecture and permeability.
The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids.
TLDR
A mutational analysis is reported that conclusively demonstrates that the conserved acyltransferase-encoding gene papA5 is essential for PGL production and establishes proof of principle for the competency of PapA5 to utilize diol-containing polyketide compounds of mycobacterial origin as acyl-acceptor substrates.
...
1
2
3
4
5
...