posted on 2021-09-20, 17:37authored byYaqian Yan, Haoxin Wang, Yuliang Song, Deyu Zhu, Yuemao Shen, Yaoyao Li
Polycyclic tetramate macrolactams
(PoTeMs) are a family of natural
products containing a tetramic acid moiety and a polycyclic 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.