Agrocybe aegerita Serves As a Gateway for Identifying Sesquiterpene Biosynthetic Enzymes in Higher Fungi

Abstract

Terpenoids constitute a structurally diverse group of natural products with wide applications in the pharmaceutical, nutritional, flavor and fragrance industries. Fungi are known to produce a large variety of terpenoids, yet fungal terpene synthases remain largely unexploited. Here, we report the sesquiterpene network and gene clusters of the black poplar mushroom Agrocybe aegerita. Among 11 putative sesquiterpene synthases (STSs) identified in its genome, nine are functional, including two novel synthases producing viridiflorol and viridiflorene. On this basis, an additional 1133 STS homologues from higher fungi have been curated and used for a sequence similarity network to probe isofunctional STS groups. With the focus on two STS groups, one producing viridiflorene/viridiflorol and one Δ6-protoilludene, the isofunctionality was probed and verified. Three new Δ6-protoilludene synthases and two new viridflorene/viridiflorol synthases from five different fungi were correctly predicted. The study herein serves as a fundamental predictive framework for the discovery of fungal STSs and biosynthesis of novel terpenoids. Furthermore, it becomes clear that fungal STS function differs between the phyla Ascomycota and Basidiomycota with the latter phylum being more dominant in the overall number and variability. This study aims to encourage the scientific community to further work on fungal STS and the products, biological functions, and potential applications of this vast source of natural products.

Systems biology approaches integrated with artificial intelligence for optimized metabolic engineering

“…One interesting and popular area of industrially relevant metabolic engineering product in the food and consumer care industries are the terpenes and terpenoids; secondary metabolites or organic compounds naturally found in diverse living species, especially in plants. Due to their high commercial values, numerous researches have focused on producing them or their derivatives at industrial scale using microbes [ [116] , [117] , [118] , [119] ]. Although several hundreds, or even thousands, of fold increase has been achieved at test tube or flask level by engineering microbes, the achievement at large industrial scale bioreactors are far from reality.…”

Natural Products from Endophytic Fungi Associated with Rubiaceae Species

“…Fungi secondary metabolites are categorized in chemical classes: polyketides [ 56 , 57 , 58 , 59 ], non-ribosomal peptides [ 57 , 59 , 60 , 61 , 62 ], ribosomal peptides [ 62 , 63 , 64 ], terpenes [ 65 , 66 , 67 ], and hybrid metabolites [ 68 , 69 , 70 , 71 , 72 , 73 , 74 ]. These chemical classes are synthesized by specialized class-defining (backbone) enzymes such as polyketides synthases (PKSs), non-ribosomal peptide synthetases (NRPSs), terpene cyclases (TCs), and dimethylallyl tryptophan synthases (DMATSs), respectively.…”

Bioinformatics-Aided Identification, Characterization of Fungal Linalool Synthases and Applications in Linalool biosynthesis

“…As Agrocybe aegerita is known to produce linalool and its genome has been recently sequenced 21 , we tried to identify the LS in its genome. In our previous study, we identified 11 putative sesquiterpene synthases and nine of them are functional and produced various sesquiterpenes but not linalool 3 . A re-evaluation of the raw genomic data led to an additional putative terpene synthase sequence (AAE3_109435).…”

“…Terpene synthases are pivotal for the biosynthesis and diversity of terpenoids (>80000 different molecules), which constitute the largest group of natural products 1 . Terpenoids have wide applications, including pharmaceuticals, nutraceuticals, flavorings, fragrances, and biofuels 2,3 . However, the biosynthesis of most terpenoids has yet to achieve high titers and yields that are vital for commercial production.…”