期刊
ACS SYNTHETIC BIOLOGY
卷 10, 期 9, 页码 2159-2166出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.1c00309
关键词
olivetolic acid; fungal pathway; cannabinoids; resorcylic acid; polyketide synthase; genome mining
资金
- NIH [R35GM118056]
- California NanoSystems Institute
- Noble Family Innovation Fund
- National Science Foundation (NSF) [DMR-1933487]
- NSF [CHE-1048804]
A set of fungal tandem polyketide synthases has been discovered to produce high titers of olivetolic acid and related derivatives, which could enable new synthetic biology strategies for accessing microbial cannabinoids.
The microbial synthesis of cannabinoids and related molecules requires access to the intermediate olivetolic acid (OA). Whereas plant enzymes have been explored for E. coli and yeast biosynthesis, moderate yields and shunt product formation are major hurdles. Here, based on the chemical logic to form 2,4-dihydroxybenzoate-containing natural products, we discovered a set of fungal tandem polyketide synthases that can produce OA and the related octanoyl-primed derivative sphaerophorolcarboxylic acid in high titers using the model organism Aspergillus nidulans. This new set of enzymes will enable new synthetic biology strategies to access microbial cannabinoids.
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