Phylogeny Of Polyene Macrolide Antibiotic Biosynthetic Genes

Antibiotic biosynthetic genes cluster together to improve protein expression, butthe origin of antibiotic gene clusters and how related genes cluster together are stillunknown. The polyene macrolide (PEM) family is one of the most efficient groups ofantifungal drugs. PEMs share similar structures and have a close evolutionaryrelationship, which makes them suitable to elucidate the evolution of polyketideantibiotic gene clusters.In this study, we used phylogenetic analyses, GC content differences, and codonusage and conserved sites comparison to trace the origins of PEM biosynthetic genesand investigate the evolutionary differences among these genes. In this paper, severalmethods including sequence based phylogeny, structure based phylogeny, GC contentdifferences, codon usage and conserved site comparison were used.The study showed that PEM polyketide synthases (PKSs) shared a commonancestor from Actinobacteria. Corresponding domains of non-glycosylated PEMPKSs and GPEM PKSs diverged from each other after their last common ancestor.Some GPEM PKS genes were orthologs and others had arisen through geneduplication. PEM P450s had a close evolutionary relationship with those fromactinobacterial organisms: group I P450s were derived from Actinobacteria, exceptStreptomyces, whereas group II P450s were derived from Streptomyces.Non-glycosylated PEM P450s might also be derived from Streptomyces, but theirancestor was different from that of GPEM P450s. GPEM sugar moietybiosynthesis-related enzymes were similar to their homologues from various phyla orkingdoms and might have been acquired through horizontal gene transfers (HGT).Four different groups of GPEM ATP-binding cassette transporters clustered withthose from actinobacterial organisms. Three groups of PEM regulators had a closeevolutionary relationship with the homologues from Streptomyces. The resultssuggest that different genes in the PEM biosynthetic gene cluster may not have thesame origin. In PEM biosynthetic gene cluster, enzymes maintaining basic structureof antibiotic like PKSs were required as a whole, while tailoring enzymes has beenformed by obtaining recruiting the relevant genes step by step from various sourcesthrough evolution.