Biocatalytic and chemical derivatization of the fungal meroditerpenoid chevalone E

Abstract

Fungal meroditerpenoids include diverse molecules with structural complexity and a broad range of biological activities. We have previously obtained meroditerpenoid chevalone E (1) and its oxidized analogues by heterologously expressing...

Recent developments in the engineered biosynthesis of fungal meroterpenoids

“…Among the novel compounds isolated from the production system, some exhibited intruiging pharmacological activities, such as antitumor ( 16), anti-HIV activity (17), and anti-Alzheimer's disease properties (18). Furthermore, FMO EsdpE, which epoxidizes the C-14, C-15 double bond of 13, was employed to produce 19, and the CYC EsdpB cyclizes in a chair-chair-chair conformation to form the 6-6-6 ring structure of 20 [18,19]. This difference in the epoxidation position represents a new point of biosynthetic diversity that will receive keen attention in the future.…”

Structure-based engineering of α-ketoglutarate dependent oxygenases in fungal meroterpenoid biosynthesis

“…Finally, the engineered enzymes can be utilized in combinatorial biosyntheses in heterologous expression hosts such as Aspergillus oryzae, to produce pharmaceutically useful molecules, as demonstrated by the recent successful productions of unnatural novel diterpene fungal meroterpenoids. [64][65][66] Therefore, the discovery, engineering, and reconstitution of fungal meroterpenoid oxidation pathway will continue to provide important insight into natural product chemistry and enzymology, and will lead to the production of benecial drugs.…”

Synthetic Biology Tools for Engineering Aspergillus oryzae

“…Capitalizing on a robust capacity for protein synthesis, secretion, and posttranslational modification, A. oryzae has also shown potential for heterologous protein expression. Recently, the integration of heterologous pathways into the A. oryzae genome through precise genetic manipulation has yielded a diverse array of enzymes and secondary metabolites, exemplified by ergothioneine [5], orsellinic acid [6], chevalone E [7], abscisic acid [8], aphidicolin [9], and others. As genetic manipulation techniques continue to evolve, the utilization of A. oryzae as a host for heterologous protein expression is increasingly maturing.…”