Wu Peiling, Chen Haofeng, Chen Yueyang, Zhang Yang, Yuan Jifeng
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China.
Shenzhen Research Institute of Xiamen University, Shenzhen, Guangdong, China.
Nat Commun. 2025 May 16;16(1):4568. doi: 10.1038/s41467-025-59753-8.
Microbial synthesis of chemicals using renewable feedstocks has gained interest due to its sustainability. The class of β,γ-diols has unique chemical and physical properties, making them valuable for diverse applications. Here, we report a biosynthetic platform in Escherichia coli for the synthesis of branched-chain β,γ-diols from renewable feedstocks. Firstly, we identify an acetohydroxyacid synthase from Saccharomyces cerevisiae to catalyze the condensation of branched-chain aldehydes with pyruvate, forming α-hydroxyketones. Next, de novo production of branched-chain β,γ-diols (4-methylpentane-2,3-diol, 5-methylhexane-2,3-diol and 4-methylhexane-2,3-diol) is realized from branched-chain amino acids (BCAA) metabolism. After systematic optimization of the BCAA pathway, we have achieved high-specificity production of 4-methylpentane-2,3-diol from glucose, achieving 129.8 mM (15.3 g/L) 4-methylpentane-2,3-diol with 72% of the theoretical yield. In summary, our work demonstrates the synthesis of structurally diverse branched-chain β,γ-diols, highlighting its potential as a versatile carbon elongation system for other β,γ-diol productions.
利用可再生原料进行化学品的微生物合成因其可持续性而受到关注。β,γ-二醇类具有独特的化学和物理性质，使其在多种应用中具有价值。在此，我们报道了一种在大肠杆菌中构建的生物合成平台，用于从可再生原料合成支链β,γ-二醇。首先，我们从酿酒酵母中鉴定出一种乙酰羟酸合酶，以催化支链醛与丙酮酸的缩合反应，形成α-羟基酮。接下来，通过支链氨基酸（BCAA）代谢实现了支链β,γ-二醇（4-甲基戊烷-2,3-二醇、5-甲基己烷-2,3-二醇和4-甲基己烷-2,3-二醇）的从头合成。在对BCAA途径进行系统优化后，我们实现了从葡萄糖高效特异性生产4-甲基戊烷-2,3-二醇，4-甲基戊烷-2,3-二醇产量达到129.8 mM（15.3 g/L），理论产率为72%。总之，我们的工作展示了结构多样的支链β,γ-二醇的合成，突出了其作为用于其他β,γ-二醇生产的通用碳链延伸系统的潜力。
