Cyclodepsipeptide Biosynthesis in Fungi and Sequence Divergence of The .

Fungi from the order synthesize a range of toxic non-ribosomal cyclic peptides with antimicrobial, insecticidal and cytotoxic activities. Entomopathogenic , and as well as phytopathogenic spp. are known producers of beauvericins (BEAs), beauvenniatins (BEAEs) or enniatins (ENNs). The compounds are synthesized by beauvericin/enniatin synthase (BEAS/ESYN1), which shows significant sequence divergence among members. We investigated ENN, BEA and BEAE production among entomopathogenic (, , ) and phytopathogenic () fungi; BEA and ENNs were quantified using an LC-MS/MS method. Phylogenetic analysis of partial sequences of putative / amplicons was also made. Nineteen fungal strains were identified based on sequence analysis of amplified ITS and -1α regions. BEA was produced by all investigated fungi, with and being the most efficient producers. ENNs were synthesized mostly by , and . The phylogeny reconstruction suggests that ancestral BEA biosynthesis independently diverged into biosynthesis of other compounds. The divergent positioning of three isolates raises the possibility of parallel acquisition of cyclic depsipeptide synthases in ancient complexes within genus. Different fungi have independently evolved NRPS genes involved in depsipeptide biosynthesis, with functional adaptation towards biosynthesis of overlapping yet diversified metabolite profiles.