The molecular mechanism, regulatory mechanism and biological function of cyclosporine synthesis of wormgrass asexual puffy neck mold.

On October 2nd, the international academic journal mBio published a research paper entitled Cyclosporine biosynthesis in Tolycladpoium inflated benefitstoe to the environment.
the work reported on the molecular mechanism, regulatory mechanism and biological function of cyclosporine, which is asexual of insect grass puffing neck mold, etc.
broad-based insect sphers, including pest-resistant fungi, can synthesize small molecular compounds with various structures, but the synthesis mechanism of different compounds and their mediated biological functions are not clear. Prior research by Wang Chengshu Research Group of
revealed that the synthetic destruxins (destruxins; PNAS, 2012), and the white-frozen bacteria synthetic osporein (osporein); PNAS, 2015), as well as the molecular mechanisms of the synthetic serocosin (cordycepin) and pentostatin (Cell Chem Biol, 2017), as well as the insecticidal or antibacterial activity mediated by different compounds, promote the chemical biology of broad-based insect-based fungi.
cyclosporine (also known as cyclosporine or cyclosporine) is a non-ribosome cyclogenous polypeptide consisting of 11 normal and abnormal amino acids, which were first isolated and identified in 1971, and more than 30 structural analogues have been found.
, cyclosporine A (CsA), which has antifungal activity, was approved by the FDA in 1983 as an anti-immune rejection commodity drug, but the complete synthesis mechanism of the compound has been unclear. After analyzing the genomic information of the bent neck mold, Yang Xiuqing, a doctoral student in wang Chengshu Research Group of
, carried out a series of experiments on gene deletion, intermediate product isolation identification and substrate feeding feeding, and analyzed the synthesis mechanism of cyclosporine, which contained the gene clusters of non-ribosome polypeptide synthesis NRPS (SimA) and polyketone synthase PKS (SimG).
prove that the SimG pathway in the gene cluster is responsible for the synthesis of the abnormal amino acid 2-butene-4-methyl-suline Bmt, the muffin SimB is responsible for converting L-alanine into D-type alanine, and then the order of the 11 substrates mediated by SimA to add and cyclicize to produce CsA.
studies have also revealed that bZIP type transcription factor SimL regulates gene cluster gene expression and product synthesis, and cyclophilin (cyclophilin) SimC and extracellular transporter SimD are involved in protecting the cell toxins caused by the production of bacteria synthesis CsA.
biometrics have shown that the synthesis of CsA can help produce bacteria that are inthegate to other fungi in the environment, while promoting insecticidal activity of bent neck mold.
the work systematically analyzes the biosynthesis and its regulatory mechanism of cyclosporine, which further proves that secondary metabolites of fungal synthesis have important biological functions for the production of bacteria.
the study was funded by the National Fund Committee and the Chinese Academy of Sciences Strategic Leader B.
Source: Shanghai Institute of Life Sciences.