期刊
ACS SYNTHETIC BIOLOGY
卷 10, 期 10, 页码 2434-2439出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.1c00178
关键词
polycyclic tetramate macrolactam; cytochronte P450; combinatorial biosynthesis; natural products
资金
- NSFC [81773598]
- Young Scholars Program of Shandong University [2016WLJH31]
- Fundamental Research Funds of Shandong University [2018JC004]
PoTeMs are a family of natural products containing a tetramic acid moiety and a polycyclic system, displaying cytotoxic activity against human cancer cell lines. Manipulating the biosynthesis of PoTeMs by swapping modification genes between different pathways can facilitate the engineered biosynthesis of other PoTeMs in the future.
Polycyclic tetramate macrolactams (PoTeMs) are a family of natural products containing a tetramic acid moiety and a polycydic system. Due to the valuable biological activities of different PoTeMs and the genetic simplicity of their biosynthetic genes, it is highly desirable to manipulate the biosynthesis of PoTeMs by swapping modification genes between different pathways. Herein, by combining the cytochrome P450 (CYP) enzymes from different PoTeM pathways with the combamides' biosynthetic genes, the new combamides G (3), I (5), and J (6) along with the known combamides B (1), D (2), and H (4) were identified from the recombinant strains. Combamides G (3), H (4), and J (6) displayed cytotoxic activity against human cancer cell lines. Furthermore, our results demonstrated for the first time the substrate specificity of the PoTeM-related CYPs in vivo, which will facilitate the engineered biosynthesis of other PoTeMs in the future.
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