Griseocazines: Neuroprotective Multiprenylated Cyclodipeptides Identified through Targeted Genome Mining.
Jessie James Limlingan MalitChuanhai WuXueying TianWenchao LiuDuli HuangHerman H-Y SungLing-Li LiuIan D WilliamsPei-Yuan QianPublished in: Organic letters (2022)
Prenylation can impart pharmacological advantages to bioactive compounds. Global genome mining for prenylated cyclodipeptides identified a gczABC BGC from Streptomyces griseocarneus 132 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.