Huang Dan, Wang Xin, Liu Wei-Bing, Ye Bang-Ce
Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Bioresour Technol. 2023 Nov;388:129800. doi: 10.1016/j.biortech.2023.129800. Epub 2023 Sep 23.
Dencichine, a sought-after compound in the medical industry, requires a more efficient and sustainable production method than the current plant extraction process. This study successfully remodeled the metabolic pathway of Corynebacterium glutamicum to produce dencichine from the precursors of L-2,3-diaminopropionate (L-DAP) and oxalyl-coenzyme A. Firstly, a synthetic pathway for L-DAP was established by introducing exogenous enzymes ZmaU/ZmaV. This resulted in a production of 628 mg/L by overexpressing key genes and reducing the endogenous competitive pathway. Secondly, an oxalyl-CoA synthetic pathway was created through the enzymatic conversion of glyoxylate by introducing heterologous enzymes. Finally, with the integration of the exogenous enzyme BAHD, de novo synthesis of dencichine in C. glutamicum was achieved, and production reached 31.75 mg/L within 48-hour fermentation. This achievement represents the first successful biosynthesis of dencichine in C. glutamicum, offering a promising approach for natural product through microbial fermentation.
三七素是医药行业中备受追捧的化合物，它需要一种比目前植物提取工艺更高效、更可持续的生产方法。本研究成功重塑了谷氨酸棒杆菌的代谢途径，以便从L-2,3-二氨基丙酸（L-DAP）和草酰辅酶A的前体生产三七素。首先，通过引入外源酶ZmaU/ZmaV建立了L-DAP的合成途径。通过过表达关键基因并减少内源性竞争途径，这使得产量达到了628mg/L。其次，通过引入异源酶将乙醛酸进行酶促转化，创建了草酰辅酶A合成途径。最后，通过整合外源酶BAHD，在谷氨酸棒杆菌中实现了三七素的从头合成，在48小时发酵内产量达到了31.75mg/L。这一成果代表了三七素在谷氨酸棒杆菌中的首次成功生物合成，为通过微生物发酵生产天然产物提供了一种有前景的方法。
