Biosynthesis of depsipeptides with a 3-hydroxybenzoate moiety and selective anticancer activities involves a chorismatase
Yaoyao Shen, Fan Sun, Liu Zhang, Yijia Cheng, Hongrui Zhu, Shuping Wang, Wei‐Hua Jiao, Peter F. Leadlay, Yongjun Zhou, Hou‐Wen Lin
Abstract
gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS-PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.
Topics & Concepts
Nonribosomal peptideDepsipeptidePolyketide synthasePolyketideBiosynthesisBiochemistryGene clusterBiologyMoietyChemistryStereochemistryGeneMicrobial Natural Products and BiosynthesisGenomics and Phylogenetic StudiesCarbohydrate Chemistry and Synthesis