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Griseocazines: Neuroprotective Multiprenylated Cyclodipeptides Identified through Targeted Genome Mining

Authors :
Malit, Jessie James Limlingan
Wu, Chuanhai
Tian, Xueying
Liu, Wenchao
Huang, Duli
Sung, Herman H.-Y.
Liu, Ling-Li
Williams, Ian D.
Qian, Pei-Yuan
Source :
Organic Letters; April 2022, Vol. 24 Issue: 16 p2967-2972, 6p
Publication Year :
2022

Abstract

Prenylation can impart pharmacological advantages to bioactive compounds. Global genome mining for prenylated cyclodipeptides identified a gczABCBGC from Streptomyces griseocarneus132 containing a cyclodipeptide synthase and two prenyltransferase genes. Subsequent heterologous expression allowed isolation and characterization of griseocazines, which displayed potent neuroprotective activity. Further biotransformation analyses revealed that prenyltransferases GczB and GczC catalyzed the stereospecific prenylation of cWW and attached geranyl and farnesyl groups to a cyclodipeptide scaffold, respectively.

Details

Language :
English
ISSN :
15237060 and 15237052
Volume :
24
Issue :
16
Database :
Supplemental Index
Journal :
Organic Letters
Publication Type :
Periodical
Accession number :
ejs59459076
Full Text :
https://doi.org/10.1021/acs.orglett.2c00745