Chinese Journal of Organic Chemistry ›› 2022, Vol. 42 ›› Issue (5): 1557-1561.DOI: 10.6023/cjoc202110001 Previous Articles     Next Articles


新多环特特拉姆酸大环内酰胺3-Hydroxycombamide I的发现

颜雅倩a, 王浩鑫b, 李瑶瑶a,*()   

  1. a 山东大学药学院 天然产物化学生物学教育部重点实验室 济南 250012
    b 山东大学 微生物技术国家重点实验室 山东青岛 266237
  • 收稿日期:2021-10-02 修回日期:2022-01-14 发布日期:2022-01-20
  • 通讯作者: 李瑶瑶
  • 基金资助:
    国家自然科学基金(81773598); 山东大学青年学者计划(2016WLJH31); 长江学者和创新团队发展计划(IRT_17R68)

Discovery of a New Polycyclic Tetramate Macrolactam 3-Hydroxycombamide I

Yaqian Yana, Haoxin Wangb, Yaoyao Lia()   

  1. a Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012
    b State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237
  • Received:2021-10-02 Revised:2022-01-14 Published:2022-01-20
  • Contact: Yaoyao Li
  • Supported by:
    National Natural Science Foundation of China(81773598); Young Scholars Program of Shandong University(2016WLJH31); Program for Changjiang Scholars and Innovative Research Team in University(IRT_17R68)

3-Hydroxycombamide I (2), a new polycyclic tetramate macrolactam (PoTeM) bearing a 5/5/6 cyclization pattern was isolated from the recombinant strain S001-cbm-OX4-ikaD, which is derived from Streptomyces sp. S001 by integration of the modified combamides biosynthetic gene cluster. The chemical structure of 2 was determined by analysis of 1D and 2D-NMR and HRMS data. The hydroxylation of compound 2 at C-3 was deduced to be catalyzed by a hydroxylase of Streptomyces sp. S001. The antibacterial and cytotoxic activity of compound 2 was evaluated by filter paper disc diffusion and methyl thiazolyl tetrazolium (MTT) assay, respectively. The effect of compound 2 on inhibition of the T3SS (type III secretion system) of Salmonella enterica serovar Typhimurium was also investigated. However, compound 2 was inactivity in all assays. The results indicated that the hydroxylation at C-3 may occurs after the oxidative modifictions of the polycyclic system in the biosynthesis of PoTeMs.

Key words: natural products, biotransformations, Streptomyces, polycyclic tetramate macrolactams