Synthetic Biology-Based Discovery of Diterpenoid Pyrones from the Genome of <i>Eupenicillium shearii</i>

Abstract

Diterpenoid pyrones are a type of mainly fungal meroterpenoid metabolite consisting of a diterpene connected to a pyrone, some of which show potent bioactivity. Through genome mining and heterologous expression, nine new diterpenoid pyrones, shearones A-I (<b>1</b>-<b>9</b>), were discovered from the fungus <i>Eupenicillium shearii</i> IFM 42152, and their biosynthetic enzyme activities were revealed. Some of these heterologously biosynthesized diterpenoid pyrones exhibited moderate antiaggregative ability against amyloid β42 in vitro.