Elucidating hydroxylation and methylation steps tailoring piericidin A1 biosynthesis
Yaolong Chen1, Wenjun Zhang, Yiguang Zhu
1Key Laboratory of Tropical Marine Bio-resources and Ecology, RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences , 164 West Xingang Road, Guangzhou 510301, China.
Organic Letters
|January 14, 2014
Summary
Researchers identified the piericidin A1 gene cluster from deep-sea bacteria. Experiments revealed PieE as a hydroxylase and PieB2 as a methyltransferase, clarifying biosynthesis steps for this compound.
Area of Science:
- Natural Product Chemistry
- Microbiology
- Molecular Biology
Background:
- Streptomyces species are prolific producers of bioactive secondary metabolites.
- Piericidin antibiotics are known for their biological activities, but their biosynthesis pathways require further elucidation.
Purpose of the Study:
- To identify the gene cluster responsible for piericidin A1 biosynthesis in Streptomyces sp. SCSIO 03032.
- To characterize the enzymatic functions of key genes (PieE and PieB2) involved in post-PKS modifications.
- To identify novel analogues of piericidin A1.
Main Methods:
- Genomic analysis to identify the piericidin A1 gene cluster.
- In vivo and in vitro enzymatic assays to determine the function of PieE and PieB2.
- Structure elucidation of metabolites using spectroscopic methods.
Main Results:
- The piericidin A1 gene cluster was successfully identified in Streptomyces sp. SCSIO 03032.
- PieE was confirmed as a 4'-hydroxylase and PieB2 as a 4'-O-methyltransferase, detailing crucial post-PKS modification steps.
- A novel shunt metabolite, piericidin E1, featuring a C-2/C-3 epoxy ring, was discovered.
Conclusions:
- The study elucidated key enzymatic steps in piericidin A1 biosynthesis, involving PieE and PieB2.
- The discovery of piericidin E1 expands the known structural diversity of piericidin analogues.
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