| Secondary metabolites are a class of compounds synthesized by microorganisms to adapt to the environment.These compounds often have certain biological toxicity and are important sources of drugs.Genomics reveals that there are silent genes in microorganisms such as fungi that are hardly expressed in conventional culture,so it is more difficult to find novel structures from "ordinary" fungi using conventional methods,especially the novelty of skeleton structure,and it has also shown that the development of secondary metabolites of microorganisms such as common fungi is not thorough.At present,there are two main ways to increase the richness of secondary fungi of the same species: the first is to activate the silencing gene by molecular manipulation,thereby inducing the synthesis of new secondary metabolites,but this method has higher technical requirements and a longer development cycle.And the second stage is the OSMAC strategy,which is a multi-product strategy,which affects the level of metabolic pathways and the overall level of the culture system by relatively simp le changes in the morphology of the medium,the composition of the medium or the addition of inhibitory enzymes and stimulants.The secondary metabolism of microorganisms,although the method is weakly targeted,its operation is simple,the development cyc le is short,and the capital investment is small.Based on the analysis of known products of Myceliophthora thermophilum,it is found that the products isolated from the bacteria contain tetramic acid struct ure.The synthesis of this structure requires the participation of amino acids,bas ed on the OSMAC strategy.New compounds were discovered by adding different kinds of amino acid substrates.The crude extract of mycelium was isolated and purified by positive and negative reverse phase chromatography,Sep hadex LH-20 gel and reversed-phase high performance liquid chromatography(HPLC).Six c ompounds were obtained: 20-Methylthio-21R-Myceliothermophins A(A),20-Meth ylt-hio-21S-Myceliothermophins B(B),Myceliothermophins E(C),ergosta-4,6,8,22E-tetra-en-11?-ol(E),ergosterol(F)and a new sterol compound(EQ).Among th em,compounds A and B are methionine-stimulated to produce new compounds,a nd their synthesis mechanism is L-methionine in Myceliophthora thermophila,whi ch generates methyl mercaptan after decomposition of methionine,and methyl me rcaptan.Spontaneous attack on carbon atoms of ?,?-unsaturated ketones.Comp B and Comp C were found to have strong cytotoxicity by preliminary activity exp eriments.In addition,a strain of L059-1 was screened from the fungi from the South China Sea and identified as Aspergillus terreus by the strain.While using the la boratory for conventional liquid fermentation,the medium morphology and compo sition were changed based on the OSMAC strategy,using rice medium and a ser ies of optimized media,respectively.By comparison,it was found that the secon dary metabolites in the rice medium and the magnesium salt-added fermentation changed greatly,and a new peak was found on the HPLC.At present,four com pounds have been isolated in conventional culture and confirmed by structure ide ntification as Terrein,Butyrolactone-II,Butyrolactone-V and Butyrolactone-I. |
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