Unusual chemistries in fungal meroterpenoid biosynthesis

Abstract

Meroterpenoids are polyketide and terpenoid hybrid natural products with remarkable biological activities. Recent progress in fungal meroterpenoid biosynthesis has revealed several unusual enzyme reactions and novel enzymes, including unique terpene cyclization reactions by a novel family of membrane-bound terpene cyclases and post-cyclization modification reactions by oxygenases, such as non-heme iron-dependent dioxygenases, flavin adenine dinucleotide-dependent monooxygenases, and cytochrome P450 monooxygenases. They contribute to the structural diversification and increase in complexity of fungal meroterpenoids. Structure-function studies of these enzymes provide strategies for engineering the biosynthetic machinery to create novel molecular scaffolds for drug discovery.