Biochemical analysis uncovers enzymatic mechanisms of atlantinone B biosynthesis in Penicillium chrysogenum, indicating potential pathways for combinatorial drug discovery.
The biosynthetic gene cluster of atlantinone B ( 10 ) was discovered in Penicillium chrysogenum MT-40. A multifunctional cytochrome P450 (AtlD) encoded by the cluster is responsible for the formation of the unique lactone-bridged ring and the 16β-hydroxyl of atlantinone B, and a new terpene cyclase (AtlC) can unprecedentedly accept the demethylated substrate epoxyfarnesyl-DMOA ( 4a ) to generate three bicyclic meroterpenoids ( 5a – 5c ). This study paves the way for combinatorial synthesis of structurally diverse meroterpenoids for drug discovery.
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