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Professor Liu Yang’s Team succeed in demonstrate a consensus OTA biosynthetic pathway

发布时间:2018-08-25
       Recently,Professor Liu Yang’s Team has made key progress in an important mycotoxin---- Ochratoxin A biosynthetic pathway and key regulation mechanism. The study found that a gene cluster is in charge of ochratoxin A biosynthesis, and a consensus OTA biosynthetic pathway exists in all OTA-producing fungi and that is encoded by a gene cluster containing four highly conserved biosynthetic genes and a bZIP transcription factor. This is first systematically reports on the important mycotoxin---- Ochratoxin A biosynthetic pathway. Related study was published as a spotlight paper in the prestigious journal Applied and Environmental Microbiology (AEM) sponsored by American Society for Microbiology (ASM).
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       Ochratoxin A (OTA) is a significant mycotoxin that contaminates cereal products, coffee, grapes, wine, cheese and meat. OTA is nephrotoxic, carcinogenic, teratogenic and immunotoxic. OTA contamination is a serious threat to food safety, endangers human health and can cause huge economic losses. At present, more than 20 species of the genera Aspergillus and Penicillium are known to produce OTA. Here, we demonstrate that a consensus OTA biosynthetic pathway exists in all OTA-producing fungi and that is encoded by a gene cluster containing four highly conserved biosynthetic genes and a bZIP transcription factor. OTA biosynthesis begins with PKS (OtaA), utilizing acetyl-CoA and malonyl-CoA to synthesize 7-methylmellein, which is oxidized to OTβ by cytochrome P450 monooxygenase (OtaC). OTβ and L-β-phenylalanine are combined by NRPS (OtaB) to form an amide bond to synthesize OTB. Finally, OTB is chlorinated by halogenase (OtaD) to OTA. Two regulator, otaR1 and otaR2, could modulate only the expression of biosynthetic genes. . otaR1 and otaR2 both regulate OTA biosynthesis, with OtaR1 acting as the pathway specific regulator and controlling the expression of the four biosynthetic genes otaA-D. Research results identified a consensus OTA biosynthetic pathway that can be used to prevent and control OTA synthesis, and to understand variation and production of the intermediate components in the biosynthetic pathway.
       Associate Professor Dr. Yan Wang, Dr. Liuqing Wang contribuate equally as the first authors, Professor Dr. Yang Liu as the correspondence author. This work was supported by the National Key Research and Development Program of China (2017YFC1600900), National Science Foundation of China (31601577) and National Basic Research Program of China (973 program) (2013CB127800).
       Link of Journal:https://aem.asm.org/content/early/2018/07/23/AEM.01009-18