6.2.3. 1 tetraketone compound
This substance has been found in small quantities. Hartz pyridone (21) produced by Trichoderma harzianum (Dickinson et al., 1989) comes from the reaction of tetraketone with aspartic acid. The chemical structural formula is shown in Figure 6.3. Interestingly, the racemic form of hartzylpyridone was obtained first, and then its racemic form was obtained from another strain. The exact configuration of the latter needs further verification. Raceme has strong antifungal activity, and has obvious inhibitory effect on botrytis cinerea, Rhizoctonia solani and take-all disease of wheat. Wheat and Pythium Ultimate (Vinale et al., 2006), but only racemic forms are left.
6.2.3.2 pentanone
The first volatile substance isolated from Trichoderma is 6- pentyl -2 H- pyran -2- one (6- pentyl -2H- pyran -2- one) (6PP, 22), which was once used as a perfume, and was first found in Trichoderma viride, and later isolated from various Trichoderma species. 6PP produced by Trichoderma harzianum strains T 16 and T23 can inhibit the production of wilting acid, and the inhibition rates of the two strains are 32.5% and 45% respectively at the concentration of 300mg/mL (El-Hasan et al., 2008).
Fig. 6.3 Tetraketone, a Metabolite of Polyketone
At present, the biosynthetic pathway of 6PP and other substances in this group is only speculation, which may come from linoleic acid. However, the experiment of synthesizing 6PP from linoleic acid by radioisotope tracing proved that 6PP was not from linoleic acid (Ser-rano-Carreon et al., 1993). The suspension culture of Pinus radiata cells was studied. It was found that 6PP was hydroxylated in the alkyl side chain, and after 144h, it was partially transformed into 5-(2- pyran -6- yl) pentyl -5- ol [5-(2- pyran -6- yl) pentyl -5- ol].
The related dehydrogenation derivative 6-( 1'- pentenyl) -2H- pyran -2- one [6-( 1'- pentenyl) -2h- pyran -2- one] (24) also has a typical coconut fragrance, which comes from Trichoderma viride and Trichoderma koningii (T.
Trichoderma metabolites massoilactone)(25) and δ-δ-decanolide (26) can be used as microbial control factors, which have broad-spectrum antibacterial ability against plant pathogenic fungi and have been patented (Chen Kai et al., 2007). These compounds can be isolated from different Trichoderma species.
The volatile substances produced by Trichoderma viride were identified by improved HS-SPME-GC-MS method (Stoppacher et al., 20 10). The results showed that the volatile compounds were alcohols, ketones, alkanes, furans, pyranone (mainly 6PP) and sesquiterpenes, and 13 was found for the first time. A large number of substances were isolated from Trichoderma viride strain 272 and Trichoderma echinosporus strain 328 by CLSA and GC/MS, including the known alkyl or alkenyl pyrone, and a new substance (E)-6- (pent -2- ene-1- yl) -2H- pyran -2- one [(e)-6- (. 6- propyl -2H- pyran -2- one (6- propyl -2H- pyran -2- one) (28) and 6- heptyl -2H- pyran -2- one (6- heptyl -2H- pyran -2- one) (29), and propionic acid was used in the terminal reaction.
Trichoderma viride (30) isolated from Trichoderma viride fermentation supernatant can inhibit the growth of Streptomyces rosenbergii in vitro, and its minimum inhibitory concentration is 196 μ g/ml (Evident et al., 2003).
Hartz acid (3 1), a derivative of terlamic acid, was isolated from Trichoderma harzianum. The minimum inhibitory concentrations of Pasteurella multocida and Proteus mirabilis were 12.5μg/mL and 25μg/mL, respectively, showing weak resistance and acute toxicity (MIC =150mg/kg) to mice (Sawa et al., 1994), and were sensitive to Pythium irrationalum, Sclerotinia sclerotiorum and Solanum melongena. In recent years, it has been found that the acid (32) and acid (33) from strain F- 153 1 are inhibitors of esterase (PP2A) (Kawada et al., 2008).
* * * Trichoderma harzianum and Catharanthus roseus are cultured to produce pilomycin (34), which consists of cycloalkane and terlamic acid. It has significant antibacterial activity against G+ bacteria such as Staphylococcus aureus and Bacillus subtilis (Marfori et al., 2002), and it can also inhibit the rhizome growth of rice (rice), mung bean (mung bean), alfalfa (alfalfa), pepper and tomato (tomato, 2003).
Kangningmycin A ~ E (35 ~ 39) and G(40) are also from Trichoderma, and their structures have been verified by X- ray (Mori et al., 2002). These substances have different control effects on wheat chlorosis, among which Kangningning C has the best control effect. Koninginin)D has inhibitory effects on take-all pathogen of wheat, solanacearum, cinnamon take-all pathogen, Fusarium oxysporum and wheat scab (Dunlop et al. Except Koninginin, Polyketone derivatives were also found from marine fungus T.koningii: 7-O- methyl koninginin D(7-O- methyl koninginin D) (4 1) and Trichoderma A ~ D (42 ~ 45) (Song et al. 2065438+). The chemical structural formula of these metabolites is shown in Figure 6.4.
6.2.3.3 heptanone
Hartz lactone) (46) and its dehydrogenation derivative (47) are γ -butyrolactone from Trichoderma harzianum (Claydon et al.,1991; Ordentlich et al., 1992), inhibiting the germination of conidia and chlamydospores of Fusarium oxysporum. Trichoderma harzianum also produces T39 crotonic acid lactone (T39 crotonic acid lactone) (48) and T22 azaphenanthrone (49), which can inhibit the growth of tomato early blight, Fusarium oxysporum and wheat take-all fungus varieties in vitro (Vinale et al., 2006). Harziphilone)(50) and fleephilone (5 1) also came from the same strain, and the inhibition rate of Rev-RRE was 50% in 2 ~ 8 mm, but it was inactive to HIV, presumably because the substance could not enter cells (Qian-Cutrone et al., 65438+).
It was found that the inhibitory concentrations of T22 azaphenanthrone and harzbidone were only 1 ~ 10μ g/ml, while the inhibitory concentrations of T39 butenolide and harzbenolactone were higher than 100μg/mL. Although T22 azaphenanthrone has antifungal activity, the presence of pathogenic fungi can not stimulate the increase of Trichoderma T22 azaphenanthrone production. Anthraquinone itself has no antibacterial activity against fungi, but the yield of T39 butenolide has been significantly improved after inoculation with Phytophthora infestans or botrytis cinerea. It is believed that the presence of pathogenic fungi increases the accumulation of harzbinone, which was not detected in the experiment (Vinale et al., 2009a).
Two new hydroxyl lactones were named Hartz lactone) A and B(52, 53). The hydroxyl lactones from Trichoderma harz strain OPPS-N115 were R- methyl valerolactone (54) and Hartz lactone (54). R- mevalonolide can accelerate the metabolism of cholesterol in aging skin, indicating that it has anti-aging activity and can be used in cosmetics industry (Yamashita, 2000).
Fig. 6.4 Pentone, a metabolite of polyketone.
5- hydroxythulium lactone (55) is slightly different from other crotonolides, it comes from trichoderma longibrachiatum (T. Longbrachiatum) and has antibacterial activity against citrinin (Andrade et al., 1997). The chemical structural formula of these metabolites is shown in Figure 6.5.
Fig. 6.5 metabolites of heptanone and polyketone.
6.2.3.4 octaketone
Anthraquinones are well-known substances produced by Trichoderma viride, Trichoderma viride and Trichoderma polytrichum, mainly including Poria cocos (56), chrysophanol (57) and emodin (57). Emodin has monoamine oxidase and tyrosine kinase activities (Jayasuriya et al., 1992), and also has antibacterial, anti-tumor and cathartic effects, which can inhibit the growth of Gram-positive bacteria, especially Staphylococcus aureus (Chukwujekwu et al., 2006; Ali et al., 2004). Chrysophanol has antifungal activity, and its minimum inhibitory concentration (MIC) for Candida albicans, Cryptococcus neoformans, Trichophyton mentagrophytes and Aspergillus fumigatus is 25 ~ 250μ g/ml (Agarwal et al., 2000), which is similar to other substances.
Trichoderma. Trichoquinone (59) produces a large number of anthraquinones when facing Fusarium. Trichoderma viride produced compounds 1, 3,6,8-tetrahydroxyanthraquinone (1, 3,6,8-tetrahydroxyanthraquinone) (60) and 1- acetyl -2 after UV mutagenesis. 7- tetrahydroxyxanthone (6 1) is a uncoupler of mitochondrial oxidative phosphorylation (Betina et al., 1987), and its antibacterial effect is weak (Gottasovà et al., 1998). Dimethoxyxanthone isolated from Trichoderma (62) is another form of octaketone with symmetrical winding structure.
Trichoharzin)(63) was isolated from Trichoderma T.harzianum, a sponge parasite, which produced a large number of different metabolites in both salt-free and salt-containing media. This substance may be octaketone from Diels-Adler reaction. It should be similar to the synthetic route of lovastatin by Aspergillus terrestris (Witter et al., 1996), and Trichoderma longum and Trichoderma koningii produce compac-tin)(64 64 64). This substance and similar substances play an important role in lowering LDL cholesterol in patients with hypercholesterolemia (Jakobisiak et al., 2003). The chemical structural formula of these metabolites is shown in Figure 6.6.
Fig. 6.6 Octanone, a metabolite of polyketone.
6.2.3.5 nonane
Mevastatin) (65), derived from T.koningii and T.longibrachiatum, is the precursor of pravastatin) (66), and pravastatin is used as a hydroxy acid active substance in clinic (Serajuddin et al., 199 1). The chemical structural formula of this group of metabolites is shown in Figure 6.7.
Fig. 6.7 Polyketone Metabolite-Nonane
6.2.3.6 dodecanone
This kind of substance has special biological activity, and is named bisorbicillinoids or bisvertinoids. Mainly produced by Trichoderma, generally from sorbitol (67) (Andrade et al.,1992; Abe et al., 1998 b), whose derivative is sorbitol (68) (Abe et al., 2000a). Other derivatives include desmethyl sorbitol (69), sorbitol oxide (70) (Abe et al., 2000b) and sorbitol oxide (71) (Perry et al., 65438+).
By studying the inhibitory effect of trichoderma longibrachiatum on Mycobacterium citricum, it was found that the antibacterial activity was related to the metabolite produced by trichoderma longibrachiatum, which had a tight five-membered ring structure and was Trichoderma Diol (72) (Andrade et al.,1996; Andrade et al., 1997), whose structure is inferred by spectrum and confirmed by single crystal X-ray (advanced, 1995). In addition to trichoderma longibrachiatum, Trichoderma diol can also be isolated from Trichoderma strain USF-2690 (Abe et al., 2000a). Trichoderma glycol (Barnes-Seeman et al.,1999; Abe et al., 1998 b), the inhibitory concentration IC50 of trichodimerol diol on mouse macrophages and human monocyte tumor necrosis factor TNF-a was 600μg/mL and 4.0μg/mL, respectively. In addition, this substance also has therapeutic effect on prostate diseases (Mazzucco et al., 1996).
The demethylation derivatives of Trichoderma diol (74) and bicyclic cyclohexanone (75) also came from Trichoderma USF-2690, and then bicyclic hexenol (76) was found. Isorbibutenolide(77) and bisorbicillinolide(78)(Abe et al., 1998a, 1998b, 1999) have antioxidant activity, and bisorbicillinolide also has free radical scavenging activity (ED50 = 365438+. In addition, bisvertinolone(79)(Abe et al., 1998a) and its simplified form Bisvertinone (80) were obtained from trichoderma longibrachiatum fermentation. In addition, Bislongi quinolide (Bisorbutenolide) (Andrade et al., 1997), Trichdermolide (8 1) and sorbitol (82) (Andrade et al., 1996) were also obtained.
Bisvertinolone did not significantly inhibit the synthesis of β- 1, 3- glucan, but could inhibit the synthesis of β- 1, 6- glucan, causing the deformation of Saccharomyces cerevisiae mycelium. In addition, the structures of desmethyl sorbitol, oxo sorbitol -linol, epoxy sorbitol -linol, trichotetronine(83) and its analogues (84) obtained recently have also been confirmed by NMR and CD spectra (Sperry et al.,1998; Liu et al., 2005b). The chemical structural formula of these metabolites is shown in Figure 6.8.