Ethylene glycol is an attractive two-carbon alcohol substrate for biochemical product synthesis as it can be derived from CO₂ or syngas at no sacrifice to human food stocks. Here, we disclose a five-step synthetic metabolic pathway enabling the carbon-conserving biosynthesis of the versatile platform molecule 2,4-dihydroxybutyric acid (DHB) from this compound. The linear pathway chains ethylene glycol dehydrogenase, D-threose aldolase, D-threose dehydrogenase, D-threono-1,4-lactonase, D-threonate dehydratase and 2-oxo-4-hydroxybutyrate reductase enzyme activities in succession. We screen candidate enzymes with D-threose dehydrogenase and D-threonate dehydratase activities on cognate substrates with conserved carbon-centre stereochemistry. Lastly, we show the functionality of the pathway by its expression in an Escherichia coli strain and production of 1 g L⁻¹ and 0.8 g L⁻¹ DHB from, respectively, glycolaldehyde or ethylene glycol.

乙二醇是一种用于生化产品合成的有吸引力的二碳醇底物，因为它可以从CO ₂或合成气中衍生而不会牺牲人类食物储备。在这里，我们公开了一个五步合成代谢途径，能够从该化合物中以碳节约的方式生物合成多功能平台分子 2,4-二羟基丁酸 (DHB)。线性途径依次链接乙二醇脱氢酶、D-苏糖醛缩酶、D-苏糖脱氢酶、D-苏糖酸-1,4-内酯酶、D-苏糖酸脱水酶和2-氧代-4-羟基丁酸还原酶活性。我们在具有保守碳中心立体化学的同源底物上筛选具有 D-苏糖脱氢酶和 D-苏糖酸脱水酶活性的候选酶。最后，我们通过其在大肠杆菌菌株中的表达以及分别从乙醇醛或乙二醇产生1 g L ^-1和0.8 g L ^-1 DHB来展示该途径的功能。