Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae


Beilstein J Org Chem. 2024 Mar 20;20:638-644. doi: 10.3762/bjoc.20.56. eCollection 2024.


Fungal meroterpenoids are diverse structurally intriguing molecules with various biological properties. One large group within this compound class is derived from the aromatic precursor 3,5-dimethylorsellinic acid (DMOA). In this study, we constructed engineered metabolic pathways in the fungus Aspergillus oryzae to expand the molecular diversity of meroterpenoids. We employed the 5-methylorsellinic acid (5-MOA) synthase FncE and three additional biosynthetic enzymes for the formation of (6R,10’R)-epoxyfarnesyl-5-MOA methyl ester, which served as a non-native substrate for four terpene cyclases from DMOA-derived meroterpenoid pathways. As a result, we successfully generated six unnatural 5-MOA-derived meroterpenoid species, demonstrating the effectiveness of our approach in the generation of structural analogues of meroterpenoids.

PMID:38533468 | PMC:PMC10964032 | DOI:10.3762/bjoc.20.56