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Trichoderma specialized metabolites in biocontrol: gene-metabolite links, ecological functions, and translational bottlenecks.

Trichoderma spp. produce a diverse repertoire of metabolites with specific activities that contribute to biocontrol through direct antagonism, ecological signalling, and modulation of plant responses. However, current knowledge remains uneven: many metabolites are chemically described, whereas fewer are supported by robust gene-metabolite associations, experimentally validated ecological functions, and realistic translational evidence. Progress in this field will depend less on expanding compound catalogues than on integrating mechanistic, ecological, and translational evidence. This review examines the specialized metabolism of Trichoderma with emphasis on biosynthetic gene clusters, regulatory networks, ecological roles, and biosafety constraints relevant to biocontrol. Major metabolite classes, including polyketides, terpenoids, peptaibols, siderophores, diketopiperazines, and volatile organic compounds, are discussed together with representative case studies for which genetic and functional evidence is available. We further propose a translational framework to distinguish metabolites with mainly descriptive support from those approaching application readiness, based on four criteria: gene-level validation, demonstrated ecological role, manageable biosafety profile, and feasible delivery/stability. This perspective helps explain why metabolite inventories continue to expand faster than field translation. Recent advances in genomics, transcriptomics, metabolomics, genome editing, and formulation science are reshaping how Trichoderma metabolites are prioritized for future development.

Biosafety

Genetic and metabolite diversity of Sundaland Heptapleurum (Araliaceae) insight into evolutionary and specialized metabolite.

BACKGROUND: The genus Heptapleurum Gaertn (previously treated as Schefflera J.R.Forst. & G.Forst.) within the Araliaceae family is recognized for its significant medicinal value and complex taxonomy. However, an integrated understanding of its evolutionary and metabolite diversity remains unexplored, especially in the Sundaland region (i.e., Java and Sumatra). Here, we integrate genomics and metabolomics to unravel the evolutionary relationships and metabolite diversity of 10 Heptapleurum species from Sundaland. RESULTS: We assembled 10 new complete plastid genomes (plastomes) and 45S nuclear ribosomal DNA (nrDNA) sequences, identifying significant variation and potential key molecular markers. Metabolomics identified 152 metabolites, mainly phenolics and terpenoids. Metabolite profiles of H. rhynchocarpum and H. capituliferum were more correlated with phylogeny than with geography; these two species were separate from the main Heptapleurum clade. Four species, H. farinosum, H. longifolium, H. rigidum, and H. fastigiatum, have almost identical plastomes and 45S nrDNA structures, suggesting they may represent closely related species with different phenotypes, as evidenced by distinctive metabolite compositions. CONCLUSIONS: Crucially, there is an incongruence between the genetic and chemical phylogenies, underscoring that while chemotaxonomy reflects functional diversity, genetic data remains the definitive standard for evolutionary inference, with the potential for reclassifying H. rhynchocarpum and H. capituliferum. This study provides a foundation for future taxonomic revisions, conservation, and drug discovery of Heptapleurum.

Phylogeny

Antiestrogens and antiestrogen metabolites: preparation of tritium-labeled (+/-)-cis-3-[p-(1,2,3,4-tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxyl]-1,2-propanediol (U-23469) and characterization and synthesis of a biologically important metabolite.

The Upjohn antiestrogen (+/-)-cis-3-[p-(1,2,3,4-tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]-1,2-propanediol (2b, U 23469) has been prepared in tritium-labeled form by reduction of an unsaturated dihydronaphthalene precursor with carrier-free tritium gas over a palladium catalyst followed by alkylation with 3-iodo-1,2-propanediol. After extensive chromatographic purification, the final material was obtained with a specific activity of 13 Ci/mmol and a radiochemical purity of 94%. In vivo studies with immature rats show that [3H]2b is slowly converted to a more polar metabolite that is selectively accumulated in the nuclear fraction of the uterus where it is bound to the estrogen receptor. Chromatographic comparisons indicate that this metabolite is the demethylated analogue 2c, a compound that has an affinity for estrogen receptor more than 300 times greater than that of 2b. These studies suggest that the demethylated analogue 2c may be a biologically important metabolite of 2b that is involved in the action of this antiestrogen.

Animals

Marihuana metabolites in urine of man. VII. Excretion patterns of acidic metabolites detected by sequential thin layer chromatography.

The 11-oic acid metabolites of delta-9-tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD) can be identified presumptively in human urine using standard thin layer chromatographic procedures. Other acidic metabolites are also excreted but these are not yet identified. These acidic metabolites appear in urine soon after exposure but persist for at least 48 to 72 hours. Such long persistence does not permit their detection to be used for forensic purposes. Using only simple chemical methods, we have been able to identify presumptively the 11-oic acids of THC, CBN and CBD in the urine of persons taking these materials. A sequential thin-layer chromatography system we have devised provided the basis for this first report of such isolation without the use of labeled drug or mass spectrometric methods.

Cannabidiol

Determination of the metabolites of bezitramide in urine. II. The basic metabolite.

A high-performance liquid chromatographic method for the determination of low levels (less than 1 microgram/ml) of the basic metabolite of bezitramide, 1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one, in human urine is described. Special attention is given to the separation from the basic metabolite of droperidol, a drug frequently co-administered with bezitramide.

Analgesics

Determination of the metabolites of bezitramide in urine. I. Acidic metabolite.

Two methylation methods are compared in relation to the determination of low levels (less than microgram/ml) of the acidic metabolite of bezitramide in human urine. It was necessary to use alkali flame ionisation detector, which specifically detects nitrogen-containing compounds. Several difficulties associated with the use of this detector are described.

Analgesics

Metabolites of gentamicin-producing Micromonospora species I. Isolation and identification of metabolites.

From the cultural broth of a Micromonospora species 25 aminocyclitol antibiotics were isolated by repeated ion-exchange chromatographic processes. The main components of the metabolites were identified as gentamicin C1, C2, and C1a. The other previously reported gentamicin type antibiotics and some other degradation products including gentamicin A, B, B1, X2, sisomicin, garamine, gentamines etc., were identified by chemical, PMR, and mass spectroscopic studies. Besides these, seven new gentamicin type antibiotics were isolated and characterized.

Bacteria

[Prevention and therapy of respiratory distress syndrome in premature infants by means of bromhexine metabolite VIII. Animal experimental studies on the therapeutic efficacy of bromhexine metabolite VIII in premature respiratory distress syndrome].

In preparing a clinical study 14C-labelled bromhexine metabolite VIII was applied intraamnially in animal experiments. The distribution was measured in different maternal and fetal organs by thinlayer chromatography and autoradiography. A complete placental passage was found in both directions. An organspecific accumulation in the fetal lungs could not be demonstrated.

Ambroxol