Wu Hao, Guo Ye, Chen Lei, Chen Guiguang, Liang Zhiqun
State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi Microorganisms and Enzyme Research Center of Engineering Technology, College of Life Science and Technology, Guangxi University, Nanning, China.
Front Microbiol. 2019 Aug 22;10:1968. doi: 10.3389/fmicb.2019.01968. eCollection 2019.
This study characterized the biosynthetic pathway of the secondary metabolite 1-deoxynojirimycin (DNJ) from . The results revealed that glucose was a preferable precursor for DNJ synthesis, and its carbon skeleton underwent a C2-N-C6 cyclization reaction during synthesis. The biosynthetic pathway was related to the glycolysis pathway, and started from fructose-6-phosphate, and involved amination, dephosphorylation, oxidation, cyclization, dehydration, and reduction reaction steps, yielding DNJ. Then, based on clarified biosynthetic pathway information, precursors, analogs, and metabolism inhibitors were used as novel regulators to enhance the production of DNJ. The results demonstrated that the titer of DNJ could reach 296.56 mg/L, which was 3.3-fold higher than that of a control group (90 mg/L) when sodium citrate (0 h, 5 g/L), sorbose (0 h, 1 g/L), iodoacetic acid (20 h, 50 mg/L), and glucose (26 h, 7 g/L) were added during the fermentation process. This study provides a new understanding of the biosynthetic pathway of DNJ, and also provides an efficient strategy to regulate the production of DNJ based on this biosynthetic pathway, which is a new perspective for the regulation of other secondary metabolites.
本研究对[来源]中次生代谢产物1-脱氧野尻霉素(DNJ)的生物合成途径进行了表征。结果表明,葡萄糖是DNJ合成的优选前体,其碳骨架在合成过程中经历了C2-N-C6环化反应。该生物合成途径与糖酵解途径相关,从6-磷酸果糖开始,涉及胺化、去磷酸化、氧化、环化、脱水和还原反应步骤,生成DNJ。然后,基于已阐明的生物合成途径信息,将前体、类似物和代谢抑制剂用作新型调节剂以提高DNJ的产量。结果表明,当在发酵过程中添加柠檬酸钠(0小时,5 g/L)、山梨糖(0小时,1 g/L)、碘乙酸(20小时,50 mg/L)和葡萄糖(26小时,7 g/L)时,DNJ的产量可达到296.56 mg/L,比对照组(90 mg/L)高3.3倍。本研究为DNJ的生物合成途径提供了新的认识,也基于该生物合成途径提供了一种调节DNJ产量的有效策略,这为其他次生代谢产物的调节提供了新的视角。