Title: Phylogenomic analysis of polyketide synthase genes in actinomycetes: structural analysis of KS domains and modules of polyketide synthases

Authors: Samreen Sarwar; Mehboob Ahmed; Shahida Hasnain

Addresses: Department of Microbiology and Molecular Genetics, Quaid-e-Azam Campus, University of the Punjab, Lahore 54590, Pakistan ' Department of Microbiology and Molecular Genetics, Quaid-e-Azam Campus, University of the Punjab, Lahore 54590, Pakistan ' Department of Microbiology and Molecular Genetics, Quaid-e-Azam Campus, University of the Punjab, Lahore 54590, Pakistan

Abstract: Polyketides are complex and diverse secondary metabolites, synthesised by large multifunctional enzymes, Polyketide Synthases (PKS). The phylogenomic analysis of β-ketosynthase (KS) domains and PKSs within actinomycetes suggests the contribution of point mutations, gene duplications, horizontal gene transfer and homologous recombination in the evolution of PKSs. PKS genealogy suggested the ancestral module structure with KS-AT-ACP domain composition. KS domains showed similar core and highly variable loop regions at the dimer interface, which seems to affect the selectivity of the primer unit. In PKS modules, the linker regions comprise a significant fraction of the module. The reducing domains (ketoreductase and dehydrogenase) protrude out from the central axis of the module and also responsible for extreme variability in the final products. Thus, phylogenomic and structural analysis of PKSs can assist in the artificial reprogramming of PKSs.

Keywords: PKS; beta-ketosynthase; combinatorial biosynthesis; catalytic triad; primer unit; ketoreductase; dehydrogenase; phylogenomic analysis; polyketide synthase genes; actinomycetes; polyketide synthases; artificial reprogramming.

DOI: 10.1504/IJCBDD.2012.048281

International Journal of Computational Biology and Drug Design, 2012 Vol.5 No.2, pp.89 - 110

Received: 09 Jan 2012
Accepted: 09 Feb 2012
Published online: 05 Dec 2014 *

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