Exploration of marine natural resources in Indonesia and development of efficient strategies for the production of microbial halogenated metabolites
J Nat Med, 2022, 76 (1), 1–19
Nature is a prolific source of organic products with diverse scaffolds and biological activities. The process of natural product discovery has gradually become more challenging, and advances in novel strategic approaches are essential to evolve natural product chemistry. Our focus has been on surveying untouched marine resources and fermentation to enhance microbial productive performance. The first topic is the screening of marine natural products isolated from Indonesian marine organisms for new types of bioactive compounds, such as antineoplastics, antimycobacterium substances, and inhibitors of protein tyrosine phosphatase 1B, sterol O-acyl-transferase, and bone morphogenetic protein-induced osteoblastic differentiation. The unique biological properties of marine organohalides are discussed herein and attempts to efficiently produce fungal halogenated metabolites are documented. This review presents an overview of our recent work accomplishments based on the MONOTORI study.
Synthesis and Evaluation of Habiterpenol Analogs
Konya M, Arima S, Lee D, Ohtawa M, Shimoyama K, Fukuda T, Uchida R, Tomoda H, Yamaotsu N, Tanaka N, Nagamitsu T.
Chem Pharm Bull, 2022,70(4), 261–268
Habiterpenol is a G2 checkpoint inhibitor isolated from the culture broth of Phytohabitans sp. 3787_5. Here, we report the synthesis of new habiterpenol analogs through the total synthesis process of habiterpenol and evaluating the analogs for G2 checkpoint inhibitory activity. We investigated two different synthetic approaches for total synthesis, with intramolecular conjugate addition and Ti(III)-mediated radical cyclization as key reactions. Although the former was unsuccessful, the latter reaction facilitated stereoselective total synthesis and determination of the absolute configuration of habiterpenol. The extension of these chemistries to a structure–activity relationship (SAR) study gave new habiterpenol analogs, which could not be derived from natural habiterpenol and only be synthesized by applying the total synthesis. Therefore, this study provides important insights into SAR studies of habiterpenol.
Discovery of prescopranone, a key intermediate in scopranone biosynthesis
Demachi A, Ohte, S, Uchida, R, Shin-Ya, K, Ohshiro, T, Tomoda, H, Ikeda, H.
J Antibiot, 2022, 75(6), 305–311
A key intermediate in scopranone biosynthesis, prescopranone, accumulated in the mycelium of Streptomyces avermitilis SUKA carrying the biosynthetic gene cluster for scopranone lacking the sprT encoding the monooxygenase. The structure of prescopranone was elucidated by NMR and other spectral data. Prescopranone consists of a 2-pyranone ring with two atypical scoop-like moieties (1-ethyl-1-propenyl and 2-ethylbutyl groups), which was deduced as a product of the modular polyketide syntheses encoded by sprA, sprB, and sprC. Prescopranone inhibited bone morphogenetic protein (BMP)-induced alkaline phosphatase activity in a BMP receptor mutant cell line.
日本薬学会第142年会，名古屋，令和 4 年 3 月
Rotinsulu Sarah H. C.、八木 瑛穂、山﨑 寛之、Rotinsulu Henki、Wewengkang Defny、Sumilat Deiske、内田 龍児
放線菌 TMPU-A0287 株が生産する新規 piericidin 類の抗真菌活性
八木 瑛穂、山口 優雅、河﨑 敬子、碓氷 英莉、山﨑 寛之、内田 龍児
Tanzawaic acid A の全合成
田中 虎太郎、李 大葵、福田 隆志、内田 龍児、供田 洋、長光 亨