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Updated: Apr 19, 2026

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Isolation, structure elucidation, and total synthesis of tryptopeptins A and B, new TGF-β signaling modulators from
Yuta Tsunematsu1, Shinichi Nishimura, Akira Hattori
1Department of System Chemotherapy and Molecular Sciences and §Department of Bioorganic Medicinal Chemistry & Chemogenomics, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto 606-8501, Japan.
Abstract:
Two new microbial metabolites, tryptopeptins A (1) and B (2), were isolated from the cultured broth of Streptomyces sp. KUSC-G11, as modulators of the transforming growth factor-β (TGF-β) signaling pathway. Their chemical structures consisting of isovalerate, N-Me-L-Val, L-allo-Thr, and a tryptophan-related residue were elucidated on the basis of spectroscopic analyses, while they were unambiguously determined by total syntheses. A structure-activity relationship (SAR) study using natural and synthesized tryptopeptins revealed the importance of the α,β-epoxyketone function located at the C terminus. These new TGF-β signaling modulators would be highly useful for development of new drug leads targeting TGF-β-related diseases such as fibrosis and cancer.
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