Discovery and biosynthesis of guanipiperazine from a NRPS-like pathway
Jing Shi, Xiang Xu, Pei Yi Liu, Yi Ling Hu, Bo Zhang, Rui Jiao, Ghader Bashiri, Ren Xiang Tan, Hui Ming Ge
Abstract
cluster led to the production of two unprecedented alkaloids, guanipiperazines A and B. The NRPS-like enzyme activates two l-tyrosine molecules, reduces them to the corresponding amino aldehydes, and forms an unstable imine product. The subsequent enzymatic reduction affords piperazine, which can be morphed by a P450 monooxygenase into a highly strained compound through C-O bond formation. Further intermolecular oxidative coupling forming the C-C or C-O bond is catalyzed by another P450 enzyme. This work reveals the huge potential of NRPS-like biosynthetic gene clusters in the discovery of novel natural products.
Topics & Concepts
Gene clusterIdentification (biology)Computational biologyGeneBiosynthesisGenomeDrug discoveryBiologyGeneticsBioinformaticsBotanyMicrobial Natural Products and BiosynthesisMarine Sponges and Natural ProductsNatural product bioactivities and synthesis