Chrysoclostridium type diterpenoid compound as well as biosynthesis method and application thereof

By expressing the PrcA and PrcB genes in Aspergillus oryzae, a clostridium diterpenoid compound with a 5-8-5 tricyclic skeleton was synthesized, solving the synthesis problem of novel compounds and achieving effective protection against hepatocyte damage, showing potential for the treatment of metabolic diseases.

CN122444677APending Publication Date: 2026-07-24JINAN UNIVERSITY
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Patent Information

Application Number
CN202610658628.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-05-13
Publication Date
2026-07-24

AI Technical Summary

Technical Problem

Existing technologies are insufficient for effectively discovering and synthesizing novel clostridium diterpenoid compounds, and their application in the prevention and treatment of metabolic syndrome, metabolic fatty liver disease, liver injury, liver fibrosis, and cirrhosis is limited.

Method used

Heterologous synthesis of clostridial diterpenoids was achieved by isolating and expressing PrcA and PrcB genes from periconiasp. No.19-4-2-1 in Aspergillus oryzae. Compounds with a 5-8-5 tricyclic skeleton were synthesized by utilizing the diterpenoid cyclase encoded by the PrcA gene and the cytochrome P450 enzyme encoded by the PrcB gene.

Benefits of technology

The efficient synthesis of clostridial diterpenoids was achieved, which have good hepatoprotective effects and can significantly improve FFA-induced hepatocellular damage and lipid accumulation, providing therapeutic potential for metabolic syndrome, metabolic fatty liver disease, liver injury, liver fibrosis and cirrhosis.

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Abstract

The invention belongs to the field of genetic engineering and biosynthesis, and particularly relates to biosynthesis of diterpenoid compounds. The invention provides genes which play a key role in formation of 5-8-5 tricyclic mother nucleus and five-membered heterocycle in biosynthesis of diterpenoid compounds, the genes are respectively named as PrcA and PrcB and polypeptides coded by the genes, and the PrcA and PrcB are expressed by an aspergillus oryzae heterologous expression system. Five diterpenoid compounds with novel structures and anti-metabolism-related fatty liver disease activity are obtained. The invention provides application of the polypeptide in biosynthesis of the diterpenoid compounds, enriches a diterpenoid compound library, and provides a lead compound resource for finding new anti-metabolism-related fatty liver disease medicinal raw materials.
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