Genome Mining of the Biocontrol Agent _Trichoderma afroharzianum_ Unearths a Key Gene in the Biosynthesis of Anti-Fungal Volatile Sesquirepenoids  
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Upon recognition of phytopathogens, antagonistic _Trichoderma_ strains initiate the synthesis of bioactive compounds to mitigate attack by pathogens. For examples, the cell-wall-degrading enzymes, such glucanases, chitinases, and proteases, are able to disintegrate the conidia and mycelia of phytopathogens [4; 5]; the pepetabiols can alter the osmotic pressure of pathogen cells and inhibit the \(\beta\)-1,3-glucan synthetase activities [6]; antibiotics such trichodermin, viridin, and harzianolide counteract pathogens by inhibiting their ribosomal activities [7]; and bisvertinolone inhibits the biosynthesis of \(\beta\)-1,6-glucan of the pathogen cell wall [8]. In comparison to these soluble compounds that play roles through close contact, the volatile organic compounds (VOCs) produced by _Trichoderma_, such as pyrones and terpenoids, are a large group of carbon-based chemicals with low molecular weights, low polarities, low boiling points, and high vapor pressure, and they can break through physical barriers and spread over long distances in the air, water, and soil, providing greater advantages over other secondary metabolites of a microbial nature in preventing and controlling soil-borne diseases and food contamination [9; 10]. Moreover, the _Trichoderma_ VOCs have the biological activities of both hydrolytic enzymes and antimicrobial peptides, and they can promote plant growth, biomass production, and root development [11; 12]. For example, the _Trichoderma_ terpenoids have antibacterial, anti-fungal, inhibitory, cytotoxic, and anti-virus activities, and the 6-pentyl-\(\alpha\)-pyrone has anti-fungal activities against a wide range of phytopathogens of _Fusarium_, _Phyophthora_, _Rhizctonia_, _Macrophomina_, _Slerotium_, _Colletotrichum_, and _Cylindrocarbon_, as well as the stored grain pathogen _Aspergillus flavus_, by deconstructing their cell wall structure, altering the amino acid metabolism, causing downregulation of the ECHS1 protein, and inducing autophagy [13; 14; 15; 16]. Thus, application of the _Trichoderma_ VOCs is considered a promising biocontrol strategy for the management of plant diseases in agriculture and food contamination during storage. Thus far, a total of 253 terpenoids, including 202 sesquiterpenes, 48 diterpenes, two monoterpenes and one merotepenoid, have been isolated from _Trichoderma_ spp. since 1948, and the sesquiterpenes can be divided into nine categories based on the skeleton: cyclonerane-type, cadinane-type, caroten-type, acorane-type, trichotheceen-type, bisabolane-type, bottyane-type, dirmane-type and other sesquiterpenes [11]. The abundance of the bioactivities and skeletons of terpenoids presents complex biosynthetic pathways involving successive head-to-tail condensation, cyclization, and side-chain decoration of the linear chain of prenyl diphosphate of varying lengths (C5 and C10), which are catalyzed by terpenoid synthases/cyclases (TSs/TCs), polykteide synthases (PKSs), non-ribosomal peptide synthases (NRPSs), and PKS-NRPS hybrids [17; 18]. Thanks to sequencing technology developments, the genomes of 158 _Trichoderma_ strains have been published in the NCBI genome database ([[https://www.ncbi.nlm.nih.gov/datasets/genome/?taxon=5543](https://www.ncbi.nlm.nih.gov/datasets/genome/?taxon=5543)]([https://www.ncbi.nlm.nih.gov/datasets/genome/?taxon=5543](https://www.ncbi.nlm.nih.gov/datasets/genome/?taxon=5543)); accessed on 18 March 2025), and a large number of TSs have been annotated in 13 _Trichoderma_ spp. [11; 19]. However, only a few TSs from _Trichoderma_ have been functionally characterized and structurally resolved.