Comparative Analyses of Gene Clusters and Ks-alpha Genes Involved in the Biosynthesis of Chromomycin A3 and Mithramycin

Abstract

Chromomycin A3 and mithramycin are tricyclic antitumor compounds of aureolic acid class of polyketides, which are structurally related. Both polyketides differ in their glycosylation profiles and substitutions of sugars in their functional groups. Genetic organizations for the biosynthetic gene clusters of both polyketides were studied through antibiotics and secondary metabolite analysis shell and compared the genes involved in their polyketide and post-polyketide biosynthesis steps. Mauve application was also used for further visualization. 3D models of KSα gene for both polyketides along with two structurally similar polyketides of two different classes were also predicted and analyzed. Superimpositions of each model with template showed very low root-mean-square deviation values of 0.399 Å for chromomycin and chlortetracycline, 0.191 Å for mithramycin and polyketomycin, and 0.395 Å for chromomycin and mithramycin, respectively. Very low root-mean-square deviation values proved that there are high similarities between each query and template. It was also found that mithramycin and polyketomycin (tetracyclic quinone) have better superimposition hence more structural similarities as compared to mithramycin and chromomycin A3 and these discrepancies strongly suggest the horizontal transfer of aromatic polyketide biosynthesis genes of aureolic acid class. The current study will surely help in better classification of different classes of bacterial type II polyketides in future using KSα domains.