PMID:22072719

Citation	Goyal, R, Das, AK, Singh, R, Singh, PK, Korpole, S and Sarkar, D (2011) Phosphorylation of PhoP protein plays direct regulatory role in lipid biosynthesis of Mycobacterium tuberculosis. J. Biol. Chem. 286:45197-208
Abstract	Mycobacterium tuberculosis PhoP is essential for virulence and intracellular growth of the tubercle bacilli. Genetic evidence suggests that PhoP regulates complex lipid biosynthesis, and absence of some of these lipid molecules in a phoP mutant partly accounts for its attenuated growth in macrophages and/or mice. To investigate the mechanism of regulation, here we demonstrate the essentiality of phosphorylation of PhoP in the regulation of complex lipid biosynthesis. We show that phosphorylated PhoP activates transcription of pks2 and msl3, gene(s) encoding polyketide β-ketoacyl synthases through direct DNA binding at the upstream regulatory region(s) of the target genes. Our results identify the genetic determinants recognized by PhoP and show that activation of target genes requires interaction(s) of the phosphorylated regulator at the cognate binding sites. The fact that these sites within the regulatory region of respective genes do not bind in vitro with either unphosphorylated or phosphorylation-deficient PhoP protein is consistent with phosphorylation-dependent assembly of the transcription initiation complex leading to in vivo transcriptional activation. Together, these results reveal so far unknown molecular mechanisms of how PhoP contributes to M. tuberculosis cell wall composition by regulating complex lipid biosynthesis.
Links	PubMed PMC3247998 Online version:10.1074/jbc.M111.307447
Keywords	Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Cell Wall/genetics; Cell Wall/metabolism; Fatty Acid Synthetase Complex/genetics; Fatty Acid Synthetase Complex/metabolism; Lipids/biosynthesis; Lipids/genetics; Mycobacterium tuberculosis/genetics; Mycobacterium tuberculosis/metabolism; Phosphorylation/physiology; Response Elements/physiology; Transcription, Genetic/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MYCTU:P71814	involved_in	GO:0010628: positive regulation of gene expression	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MYCTU:P71814	involved_in	GO:0046889: positive regulation of lipid biosynthetic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MYCTU:P71814		GO:0046889: positive regulation of lipid biosynthetic process	ECO:0000315:		P		Fig. 1BC	complete CACAO 3186
MYCTU:P71814		GO:0010628: positive regulation of gene expression	ECO:0000315:		P		Fig. 2 and Fig. 3	complete CACAO 3187

References

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