Production of a δ-Lactam from Glucose through Integrating Biological and Chemical Catalysis

• 全文链接

通过整合生物和化学催化从葡萄糖生产δ-内酰胺

关键词：

来源：

ACS SUSTAINABLE CHEMISTRY & ENGINEERING

全文链接：

//agri.nais.net.cn/topic/downloadFile/63e54e2d-b11c-4c28-9bd7-8a4b88bd75a5

来源地址：

https://pubs.acs.org/doi/10.1021/acssuschemeng.4c08177

资源所属：

饲料用酶工程

类型：

学术文献

语种：

英语

原文发布日期：

2025-01-31

摘要：

We present a new strategy for the production of a δ-lactam from glucose that integrates biological production of triacetic acid lactone (TAL, 4-hydroxy-6-methyl-2H-2-one) with catalytic transformation of TAL into 6-methylpiperidin-2-one (MPO) through metabolic engineering, isomerization, amination, and catalytic hydrogenation/hydrogenolysis. We developed a sustainable and antibiotic-free fed-batch fermentation using genetically modified Rhodotorula toruloides IFO0880. This process achieved a yield of 2-hydroxy-6-methyl-4H-pyran-4-one (2H4P) at 0.05 g/g of glucose, corresponding to a 9.9 g/L titer. By adjusting the pH of the fermentation broth to 2, 2H4P was quantitatively converted into TAL. The TAL in the fermentation broth was directly converted by aminolysis into 4-hydroxy-6-methylpyridin-2(1H)-one (HMPO), which achieved an 18.5% yield with 94.3% purity. The HMPO yield was lower in the fermentation broth than in a clean feedstock (32.2%), suggesting that the biological impurities are inhibitors in this reaction. Further investigation revealed that lower pH levels and reduced TAL concentrations in the fermentation broth significantly decreased HMPO yields. Subsequently, the precipitated HMPO was filtered and dried and then subjected to the final catalytic conversion in H2O solvent, achieving a MPO yield of 91.8%. This integrated approach demonstrated the direct use of TAL in the filtered aqueous fermentation broth without the need to isolate TAL.