Biosynthesis and Assembly Logic of Fungal Hybrid Terpenoid Natural Products.

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.

Biosynthesis of Cosmosporasides Reveals the Assembly Line for Fungal Hybrid Terpenoid Saccharides.

Fungal hybrid terpenoid saccharides constitute a new and growing family of natural products with significant biomedical and agricultural activities. One representative family is the cosmosporasides, which feature oxidized terpenoid units and saccharide moieties; however, the assembly line of these building blocks has been elusive. Herein, a cos cluster from Fusarium orthoceras was discovered for the synthesis of cosmosporaside C (1) by genome mining.

Reshaping the Diversity of Oxidized Polyquinane Sesquiterpenoids by Cytochrome P450s.

Polyquinane sesquiterpenoids (PQSTs) are complex compounds with two or three fused cabocyclopentane ring systems, and the biocatalysts for direct C-H bond oxidation on these scaffolds have rarely been discovered. In this study, we discovered two versatile fungal CYP450s capable of performing diverse oxidations on seven PQST scaffolds, resulting in the generation of 20 unique products. Our findings significantly expand the diversity of oxidized PQST scaffolds and provide important biocatalysts for the selective oxidation of inert carbons of terpenoids in future research.

Set of Cytochrome P450s Cooperatively Catalyzes the Synthesis of a Highly Oxidized and Rearranged Diterpene-Class Sordarinane Architecture.

Cytochrome P450s are one of the most versatile oxidases that catalyze significant and unique chemical transformations for the construction of complex structural frameworks during natural product biosynthesis. Here, we discovered a set of P450s, including SdnB, SdnH, SdnF, and SdnE, that cooperatively catalyzes the reshaping of the inert cycloaraneosene framework to form a highly oxidized and rearranged sordarinane architecture. Among them, SdnB is confirmed to be the first P450 (or oxidase) that cleaves the C-C bond of the epoxy residue to yield formyl groups in pairs.

Chenodeoxycholic and deoxycholic acids induced positive inotropic and negative chronotropic effects on rat heart.

Bile acids are endogenous amphiphilic steroids from the metabolites of cholesterol. Studies showed that they might contribute to the pathogenesis of cardiopathy in cholestatic liver diseases. Chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) is associated with colon cancer, gallstones, and gastrointestinal disorders.

The bitter taste receptor agonist-induced negative chronotropic effects on the Langendorff-perfused isolated rat hearts.

Bitter taste receptors (Tas2rs), the members of the G-protein-coupled receptors, mediate the bitter taste and express in extra-oral tissues. Previous studies have shown that Tas2r mRNAs are expressed in the whole heart and cultured cardiomyocytes of neonatal rats. This study aimed to determine the expression of Tas2rs and their function in the adult rat hearts by using RT-qPCR techniques, Langendorff-perfused isolated hearts, and isolated sinoatrial (SA) nodes.