Biosynthesis and Assembly Logic of Fungal Hybrid Terpenoid Natural Products

• Published in: Chembiochem : a European journal of chemical biology 2024-12, Vol.25 (23), p.e202400387-n/a
• Main Authors: Yuan, Guan‐Yin, Zhang, Jin‐Mei, Xu, Yan‐Qiu, Zou, Yi
• Format: Article
• Language: English
• Subjects: Adenine; Amino acids; Assembly; Assembly logic; Biodiversity; Biological Products - chemistry; Biological Products - metabolism; Biosynthesis; Carbohydrates; Drug development; Fungi; Fungi - metabolism; Hybrid terpenoid natural products; Molecular Structure; Natural products; Oxidation; p-Hydroxybenzoic acid; Peptides; Polyketides; Polyketides - chemistry; Polyketides - metabolism; Saccharides; Terpenes - chemistry; Terpenes - metabolism
• ISSN: 1439-4227; 1439-7633; 1439-7633
• DOI: 10.1002/cbic.202400387

In recent decades, fungi have emerged as significant sources of diverse hybrid terpenoid natural products, and their biosynthetic pathways are increasingly unveiled. This review mainly focuses on elucidating the various strategies underlying the biosynthesis and assembly logic of these compounds. These pathways combine terpenoid moieties with diverse building blocks including polyketides, nonribosomal peptides, amino acids, p‐hydroxybenzoic acid, saccharides, and adenine, resulting in the formation of plenty of hybrid terpenoid natural products via C−O, C−C, or C−N bond linkages. Subsequent tailoring steps, such as oxidation, cyclization, and rearrangement, further enhance the biological diversity and structural complexity of these hybrid terpenoid natural products. Understanding these biosynthetic mechanisms holds promise for the discovery of novel hybrid terpenoid natural products from fungi, which will promote the development of potential drug candidates in the future. The incorporation of terpenoid moieties with diverse building blocks of polyketides, nonribosomal peptides, amino acids, p‐hydroxybenzoic acid, saccharides, and adenine relies on the collaboration of terpene cyclases (TCs) or prenyltransferases (PTs) with polyketide synthases (PKSs), nonribosomal peptide synthetase (NRPSs), or glycosyltransferases (GTs), these combination strategies significantly contribute to the formation of hybrid terpenoid natural products in fungi.