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Updated: Nov 9, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Global Genome Mining Reveals a Cytochrome P450-Catalyzed Cyclization of Crownlike Cyclodipeptides with
Jessie James Limlingan Malit1, Wenchao Liu1, Aifang Cheng1
1Department of Ocean Science and Hong Kong Branch of Southern Marine Science and Engineering Guangdong Laboratory, The Hong Kong University of Science and Technology, Hong Kong, China.
Abstract:
We conducted global genome mining of 162,672 bacterial genomes and identified 829 cyclodipeptide (CDP) biosynthesis gene clusters (BGC) containing a cytochrome P450 gene. Heterologous expression of BGC from Saccharopolyspora hirsuta DSM 44795 led to the identification of two novel crownlike CDPs, cyctetryptomycin A (4) and B (5), which possess unprecedented complex macrocycle and show neuroprotective activity. The two cytochrome P450s found in the BGC catalyze sequential reactions leading to the cyclization of diketopiperazine dimers.
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