Abstract：
1,2,4-Butanetriol serves as a precursor in the manufacture of diverse pharmaceuticals and the energetic plasticizer 1,2,4-butanetriol trinitrate. The study involved further modifications to an engineered Candida tropicalis strain, aimed at improving the production efficiency of 1,2,4-butanetriol. Faced with the issue of xylonate accumulation due to the low activity of heterologous xylonate dehydratase, we modulated iron metabolism at the transcriptional level to boost intracellular iron ion availability, thus enhancing the enzyme activity by 2.2-fold. Addressing the NADPH shortfall encountered during 1,2,4-butanetriol biosynthesis, we overexpressed pivotal genes in the NADPH regeneration pathway, achieving a 1,2,4-butanetriol yield of 3.2 g/L. The introduction of calcium carbonate to maintain pH balance led to an increased yield of 4 g/L, marking a 111% improvement over the baseline strain. Finally, the use of corncob hydrolysate as a substrate culminated in 1,2,4-butanetriol production of 3.42 g/L, thereby identifying a novel host for the conversion of corncob hydrolysate to 1,2,4-butanetriol.
摘要：
1,2,4-丁三醇在制造各种药物和高能增塑剂1,2,4-丁三醇三硝酸酯中用作前体。该研究涉及对工程化的热带假丝酵母菌株的进一步修改，旨在提高1,2,4-丁三醇的生产效率。面对由于异源木糖脱水酶的低活性而导致的木糖积累问题，我们在转录水平上调节铁代谢以提高细胞内铁离子的利用率，从而将酶活性提高2.2倍。解决1,2,4-丁三醇生物合成过程中遇到的NADPH短缺，我们在NADPH再生途径中过表达关键基因，1,2,4-丁三醇的产量为3.2g/L。引入碳酸钙以保持pH平衡导致产量增加4g/L，标记比基线应变提高111%。最后,使用玉米芯水解产物作为底物，最终产生3.42g/L的1,2,4-丁三醇，从而鉴定用于将玉米芯水解物转化为1,2,4-丁三醇的新宿主。
