1. Genome Mining and Metabolomics Uncover a Rare d-Capreomycidine Containing Natural Product and Its Biosynthetic Gene Cluster
- Author
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William W. Metcalf, Matthew T. Robey, Marvin M. Vega, Li Chen, James H. Tryon, Neil L. Kelleher, Jennifer C. Rote, Regan J. Thomson, Wan Cheng Phua, and Kou San Ju
- Subjects
0301 basic medicine ,Peptide ,Computational biology ,Arginine ,01 natural sciences ,Biochemistry ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Metabolomics ,Biosynthesis ,Bacterial Proteins ,Gene cluster ,Pyridoxal phosphate ,Peptide Synthases ,chemistry.chemical_classification ,Natural product ,010405 organic chemistry ,General Medicine ,Genomics ,Streptomyces ,0104 chemical sciences ,Biosynthetic Pathways ,030104 developmental biology ,Enzyme ,chemistry ,Multigene Family ,Molecular Medicine ,Heterologous expression - Abstract
We report the metabolomics-driven genome mining of a new cyclic-guanidino incorporating non-ribosomal peptide synthetase (NRPS) gene cluster and full structure elucidation of its associated hexapeptide product, faulknamycin. Structural studies unveiled that this natural product contained the previously unknown (R,S)-stereoisomer of capreomycidine, d-capreomycidine. Furthermore, heterologous expression of the identified gene cluster successfully reproduces faulknamycin production without an observed homologue of VioD, the pyridoxal phosphate (PLP)-dependent enzyme found in all previous l-capreomycidine biosynthesis. An alternative NRPS-dependent pathway for d-capreomycidine biosynthesis is proposed.
- Published
- 2020