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.

中文翻译：

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使用非植物生物合成途径在工程真菌宿主中高效生产橄榄酸和类似物

大麻素和相关分子的微生物合成需要使用中间体橄榄酸 (OA)。尽管已经探索了用于大肠杆菌和酵母生物合成的植物酶，但中等产量和分流产物形成是主要障碍。在这里，基于形成含 2,4-二羟基苯甲酸酯的天然产物的化学逻辑，我们发现了一组真菌串联聚酮化合物合成酶，它们可以使用模式生物构巢曲霉生产高滴度的 OA 和相关的辛酰基引发的衍生物球状佛尔羧酸。 . 这套新的酶将使新的合成生物学策略能够获得微生物大麻素。