Preliminary Construction Of Polyketide Synthase Database And Phylogenetic Analysis Of Polyene Polyketide Synthase

We have preliminarily constructed a new database for the polyketide antibiotic biosynthetic gene clusters. Compared with the existing two polyketide synthase databases, the new one mainly supplemented post polyketide synthase enzymes (including glycosyl transferase, glycosyl synthase, methyl transferase, etc) in the content aspect. As for the function of the new database, it will be more practical, especially for the phylogenetic analysis, it will provide more convenience, including downloading many sequences at the same time, multisequence alignment and corresponding reference index, etc. The new database will provide a good platform for combinatorial biosynthsis of new polyketide antibioticsPolyene macrolide antibiotics are one group of important antifungal drugs, which have similar chemical structures and close evolutionary relationships of biosynthetic gene clusters, so we chose polyene macrolide polyketide synthase as reseach object and used Bayesian inference, Neighbor-joining and Maximum Parsimony method respectively to reconstruct the phylogenetic trees of domains KS, AT, KR, DH . The results indicated that polyketide synthases corresponding with different structural parts of polyene macrolide molecules have different modes of evolution. What's more interesting is that the mode of polyketide synthase evolution is relevant to the conservativeness of the corresponding chemical structure and function. On the one hand, the chemical structures which are essential to the activity and selective toxicity are functional conservative; and the corresponding polyketide synthases whose sequences are conservative come from a common ancestor; the related chemical structures include glycosylated site, carboxylated site and hemiketal ring which are structurally coservative. On the other hand, the polyene region corresponding polyketide synthases evolved by intra-gene duplication, and the different number of duplications will lead to different kinds of polyene macrolide antibiotics which have different anfungal activities.Besides these, we also analyzed the reseaon why polyene macrolide antibiotics had so many structural analogs.