A Multifunctional Cytochrome P450 and a Meroterpenoid Cyclase in the Biosynthesis of Fungal Meroterpenoid Atlantinone B
Bowen Qi, Na Li, Beibei Zhang, Zekun Zhang, Wenjing Wang, Xiao Liu, Juan Wang, Takayoshi Awakawa, Pengfei Tu, Ikuro Abe, Shepo Shi, Jun Li
Abstract
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.
Topics & Concepts
ChemistryStereochemistryTerpeneCyclasePenicillium chrysogenumCytochrome P450Bicyclic moleculeBiosynthesisGene clusterRing (chemistry)Substrate (aquarium)EnzymeBiochemistryGeneOrganic chemistryOceanographyGeologyMicrobial Natural Products and BiosynthesisPlant biochemistry and biosynthesisFungal Biology and Applications