Phylogenetic analysis of antibiotic glycosyltransferases

Catalyzed by a family of enzymes called glycosyltransferases, glycosylation reactions are essential for the bioactivities of secondary metabolites such as antibiotics. Due to the special characters of antibiotic glycosyltransferases (AGts), antibiotics can function by attaching some unusual deoxy-sugars to their aglycons. Comprehensive similarity searches on the amino acid sequences of AGts have been performed. We reconstructed the molecular phylogeny of AGts with neighbor-joining, maximum-likelihood, and Bayesian methods of phylogenetic inference. The phylogenetic trees show a distinct separation of polyene macrolide (PEM) AGts and other polyketide AGts. The former are more like eukaryotic glycosyltransferases and were deduced to be the results of horizontal gene transfer from eukaryotes. Protein tertiary structural comparison also indicated that some glycopeptide AGts (Gtf-proteins) have a close evolutionary relationship with MurGs, essential glycosyltransferases involved in maturation of bacterial cell walls. The evolutionary relationship of glycopeptide antibiotic biosynthetic gene clusters was speculated according to the phylogenetic analysis of Gtf-proteins. Considering the fact that polyketide AGts and Gtf-proteins are all GT Family 1 members and their aglycon acceptor biosynthetic patterns are very similar, we deduced that AGts and the synthases of their aglycon acceptors have some evolutionary relevance. Finally, the evolutionary origins of AGts that do not fall into GT Family 1 are discussed, suggesting that their ancestral proteins appear to be derived from various proteins responsible for primary metabolism.