A new family of type III polyketide synthases in Mycobacterium tuberculosis

Saxena, Priti ; Yadav, Gitanjali ; Mohanty, Debasisa ; Gokhale, Rajesh S. (2003) A new family of type III polyketide synthases in Mycobacterium tuberculosis Journal of Biological Chemistry, 278 . pp. 44780-44790. ISSN 0021-9258

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Official URL: http://www.jbc.org/content/278/45/44780.abstract

Related URL: http://dx.doi.org/10.1074/jbc.M306714200

Abstract

The Mycobacterium tuberculosis genome has revealed a remarkable array of polyketide synthases (PKSs); however, no polyketide product has been isolated thus far. Most of the PKS genes have been implicated in the biosynthesis of complex lipids. We report here the characterization of two novel type III PKSs from M. tuberculosis that are involved in the biosynthesis of long-chain α-pyrones. Measurement of steady-state kinetic parameters demonstrated that the catalytic efficiency of PKS18 protein was severalfold higher for long-chain acyl-coenzyme A substrates as compared with the small-chain precursors. The specificity of PKS18 and PKS11 proteins toward long-chain aliphatic acyl-coenzyme A (C12 to C20) substrates is unprecedented in the chalcone synthase (CHS) family of condensing enzymes. Based on comparative modeling studies, we propose that these proteins might have evolved by fusing the catalytic machinery of CHS and β-ketoacyl synthases, the two evolutionarily related members with conserved thiolase fold. The mechanistic and structural importance of several active site residues, as predicted by our structural model, was investigated by performing site-directed mutagenesis. The functional identification of diverse catalytic activity in mycobacterial type III PKSs provide a fascinating example of metabolite divergence in CHS-like proteins.

Item Type:Article
Source:Copyright of this article belongs to American Society for Biochemistry and Molecular Biology.
ID Code:23076
Deposited On:25 Nov 2010 13:35
Last Modified:17 May 2016 06:58

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