Global Genome Mining Reveals a Cytochrome P450-Catalyzed Cyclization of Crownlike Cyclodipeptides with Neuroprotective Activity

• DOI: 10.1021/acs.orglett.1c01022
• Publication Date: 2021-04-15T00:09:19Z
• Authors: Jessie James Liml...; Wenchao Liu; Aifang Cheng; Subhasish Saha; Ling-Li Liu; Pei-Yuan Qian
• Keywords: Heterologous expression; Heterologous

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 BGC from Saccharopolyspora hirsuta DSM 44795 led to the identification two novel crownlike CDPs, cyctetryptomycin A (4) B (5), which possess unprecedented complex macrocycle show neuroprotective activity. The P450s found in catalyze sequential reactions leading cyclization diketopiperazine dimers.