Open AccessHigh-Titer Production of Olivetolic Acid and Analogs in Engineered Fungal Host Using a Nonplant Biosynthetic Pathway
Author(s) -
Ikechukwu C Okorafor,
Mengbin Chen,
Yi Tang
Publication year - 2021
Publication title -
acs synthetic biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.156
H-Index - 66
ISSN - 2161-5063
DOI - 10.1021/acssynbio.1c00309
Subject(s) - biosynthesis , polyketide , synthetic biology , aspergillus nidulans , polyketide synthase , natural product , enzyme , biology , biochemistry , yeast , metabolic engineering , computational biology , chemistry , gene , mutant
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.