Heterologous Expression of the Biosynthetic Gene Cluster for Verticilactam and Identification of Analogues

Toshihiko Nogawa, Atsutaka Terai, Keita Amagai, Junko Hashimoto, Yushi Futamura, Akiko Okano, Manabu Fujie, Noriyuki Satoh, Haruo Ikeda, Kazuo Shin-Ya, Hiroyuki Osada, Shunji Takahashi*

*この研究の対応する著者

研究成果: Article査読

7 被引用数 (Scopus)

抄録

Verticilactam and the new geometric isomers, verticilactams B and C, were produced by heterologous expression of the biosynthetic gene cluster for verticilactam using the Streptomyces avermitilis SUKA17 strain. Only verticilactam, a compound with a characteristic β-ketoamide unit within a 16-membered polyketide macrolactam conjugated with an octalin skeleton, had been previously reported having been isolated from Streptomyces spiroverticillatus JC-8444. In this report, minor verticilactam derivatives were isolated from the transformed strain, and their structures elucidated by spectral analysis. Verticilactam B was a geometric isomer at Δ17 and Δ19, and verticilactam C was the Δ19 and Δ21 isomer. In addition, the absolute configuration of verticilactam was confirmed by ECD analysis and NMR chemical shifts. The stereochemistry assignments of the hydroxy groups at C-10 and C-12 were supported by the domain organization of the polyketide synthase identified in the verticilactam gene cluster. Verticilactam showed moderate activity against the malaria parasite Plasmodium falciparum 3D7 strain with no significant cytotoxicity or antimicrobial effects.

本文言語English
ページ(範囲)3598-3605
ページ数8
ジャーナルJournal of Natural Products
83
12
DOI
出版ステータスPublished - 2020 12月 24
外部発表はい

ASJC Scopus subject areas

  • 分析化学
  • 分子医療
  • 薬理学
  • 薬科学
  • 創薬
  • 補完代替医療
  • 有機化学

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