Heterologous expression of the trichostatin gene cluster and functional characterization of N-methyltransferase TsnB8
- PMID: 32355936
- DOI: 10.1039/d0ob00617c
Heterologous expression of the trichostatin gene cluster and functional characterization of N-methyltransferase TsnB8
Abstract
Trichostatins are potent inhibitors of histone deacetylase (HDAC). In this work, a new trichostatin derivative isotrichostatin RK (1) and five known compounds trichostatin RK (2), JBIR-111 (3), 9179B (4), trichostatic acid (5) and trichostatin A (6) were isolated from marine-derived Streptomyces sp. SCSIO 40028. The biosynthetic gene cluster (tsnB) for trichostatins was identified from Streptomyces sp. SCSIO 40028 and validated by heterologous expression in Streptomyces lividans TK64. N-Methyltransferase TsnB8 was demonstrated to catalyze successive methyltransfer reactions by in vivo gene inactivation and in vitro enzyme assays.
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