Fatemeh Moosawi, Hassan Mohabatkar and Sasan Mohsenzadeh Pages 100 - 107 ( 8 )
Polyketides are secondary metabolites of microorganisms synthesized by serialized reactions of a set of enzymes called polyketide synthases (PKS). As many infectious microorganisms are acquiring tolerance to antibiotics, the need for novel medicines is increasing. Recently, various methods are being used for drug discovery, including gene manipulation for biosynthesis of antibiotics such as polyketides. Due to their importance as drugs, the volume of data on polyketides is rapidly increasing. In the present paper, by using SEARCHPKS and ASMPKS servers, domain identification, and domain organization, substrate specificity of AT domain, domain assembly and chemical moiety of three Actinomycetes i.e., Mycobacterium abscessus, Micromonospora chalcea and Streptomyces achromogenes are analyzed. So far, no secondary metabolite of any of these bacteria is known. Here, it was demonstrated that KR1, KR2 and KR3 domains from M. chalcea, KR5 domain from M. abscessus and KR6 domain from S. achromogenes could be assigned as B1-type, while KR4 domain from M. abscessus and KR7 domain from S. achromogenes could be assigned as A1 type. Substrate specificity of AT1 and AT2 of M. abscessus predicted to be malonate. AT2 domain of PKS protein from S. achromogenes also selected as malonate. Methylmalonate substrate was predicted for AT1 and AT3 domains. All of the AT domains in modules of PKS protein of M. chalcea were predicted to be specific for methylmalonate. Analysis of folding rate of these proteins showed that the logarithm of (kf) decreased in proportion to protein chain length. We have also performed a comprehensive phylogenetics analysis of AT and DH domains with FabA, FabZ and dehydratase proteins of various bacteria and secondary metabolites. The phylogenetic tree derived from these sequences reflects the long joint evolution process.
Computational prediction, polyketides, polyketide synthase, Mycobacterium abscessus, Micromonospora chalcea, Streptomyces achromogenes
Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.