Neoantimycin is an antimycin type depsipeptide natural product that has shown promising anticancer and immunosuppressive activity. The 15 membered macrolactone ring is synthesized from a hybrid non-ribosomal peptide synthetase (NRPS) polyketide synthase (PKS) pathway that is largely conserved in the 9, 12, 15 and 18 membered rings of the antimycin family. Using CRISPR/cas in the genetically tractable host, Streptomyces albus J1074, we have reconstituted the biosynthesis of neoantimycin. This has allowed for an updated annotation of the gene cluster and the biochemical characterization of the key enzymes. This heterologous host establishes a genetically accessible foundation for future work in combinatorial biosynthesis between the antimycin NRPS-PKS assembly lines as well as engineering neoantimycins with increased or altered pharmacological activity.

Engineered biosynthesis of neoantimycin depsipeptides in S. albus J1074

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.