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Chinese Journal of Organic Chemistry >

2022 , Vol. 42 >Issue 4: 1224 - 1228

DOI: https://doi.org/10.6023/cjoc202109042

NOTES

Discovery of a New Polycyclic Tetramate Macrolactam Clifednamide K

  • Jie Luo ,
  • Yaqian Yan ,
  • Haoxin Wang ,
  • Yaoyao Li
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  • 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
* E-mail:

Received date: 2021-09-26

  Revised date: 2021-12-24

  Online published: 2022-01-11

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)

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Abstract

The artificial hybrid polycyclic tetramate macrolactam (PoTeM) gene cluster was constructed through combinatory biosynthesis approach and two PoTeMs, preikarugamycin (1) and clifednamide K (2), were isolated from the recombinant strain SR111-cbmA-OX1-cftC. The chemical structures of 1 and 2 were determined to be the biosynthetic inermediate of ikarugamycin and a new 5/6 dicyclic PoTeM, respectively, by analysis of nuclear magnetic resonance spectroscopy (NMR) data and high resolution mass spectrometry (HRMS). The antibacterial activity of compounds 1 and 2 was tested by filter paper disc diffusion assay. The results showed that they were inactive at 20 μg/disc. The cytotoxicity of compounds 1 and 2 was evaluated by methyl thiazolyl tetrazolium (MTT) colorimetric method. Compound 1 showed potent antiproliferative activity against human liver (HepG-2) and breast cancer cell lines (MCF-7) with half maximal inhibitory concentration (IC50) values of 3.34 and 2.72 μmol/L, respectively, while compound 2 showed no cytotoxicity for the tested cell lines.

Key words： natural product; biological activity; polycyclic tetramate macrolactam; heterologous expression

Cite this article

Jie Luo , Yaqian Yan , Haoxin Wang , Yaoyao Li . Discovery of a New Polycyclic Tetramate Macrolactam Clifednamide K[J]. Chinese Journal of Organic Chemistry, 2022 , 42(4) : 1224 -1228 . DOI: 10.6023/cjoc202109042

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