Biochemical and genetic analysis uncovers the multi-redox enzyme pathway biosynthesizing harzianoic acids in Trichoderma asperellum, highlighting novel mechanisms for antiviral compound production.
Harzianoic acids (HAs) are polysubstituted cyclobutane sesquiterpenoids that display inhibitory effects against hepatitis C virus. Herein, we report the identification and characterization of the biosynthetic gene cluster of HA from Trichoderma asperellum. Genetic and biochemical analysis revealed an unexpected pathway to biosynthesize HA from farnesyl pyrophosphate via α-trans-bergamotene. This pathway involves three redox enzymes acting cooperatively to break down the six-membered ring of bergamotene to generate the skeleton of HA.
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Shen et al. (2026) studied this question.
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