Butanediols are widely used in the synthesis of polymers, specialty chemicals and important chemical intermediates. Optically pure R-form of 1,3-butanediol (1,3-BDO) is required for the synthesis of several industrial compounds and as a key intermediate of β-lactam antibiotic production. The (R)-1,3-BDO can only be produced by application of a biocatalytic process. Cupriavidus necator H16 is an established production host for biosynthesis of biodegradable polymer poly-3-hydroxybutryate (PHB) via acetyl-CoA intermediate. Therefore, the utilisation of acetyl-CoA or its upstream precursors offers a promising strategy for engineering biosynthesis of value-added products such as (R)-1,3-BDO in this bacterium. Notably, C. necator H16 is known for its natural capacity to fix carbon dioxide (CO₂) using hydrogen as an electron donor. Here, we report engineering of this facultative lithoautotrophic bacterium for heterotrophic and autotrophic production of (R)-1,3-BDO. Implementation of (R)-3-hydroxybutyraldehyde-CoA- and pyruvate-dependent biosynthetic pathways in combination with abolishing PHB biosynthesis and reducing flux through the tricarboxylic acid cycle enabled to engineer strain, which produced 2.97 g/L of (R)-1,3-BDO and achieved production rate of nearly 0.4 Cmol Cmol⁻¹ h⁻¹ autotrophically. This is first report of (R)-1,3-BDO production from CO₂.

丁二醇广泛用于合成聚合物、特种化学品和重要的化学中间体。1,3-丁二醇 (1,3-BDO) 的光学纯R型是合成多种工业化合物和生产 β-内酰胺抗生素的关键中间体所必需的。( R )-1,3-BDO 只能通过应用生物催化过程生产。Cupriavidus necator H16 是一种成熟的生产宿主，用于通过乙酰辅酶 A 中间体生物合成可生物降解的聚合物聚 3-羟基丁酸酯 (PHB) 。因此，利用乙酰辅酶A或其上游前体为高附加值产品的工程生物合成提供了一种有前景的策略，例如（R)-1,3-BDO 在该细菌中。值得注意的是，C. necator H16 以其使用氢作为电子供体固定二氧化碳 (CO ₂ ) 的天然能力而闻名。在这里，我们报告了这种兼性岩石自养细菌的工程，用于异养和自养生产 ( R )-1,3-BDO。( R )-3-羟基丁醛-CoA-和丙酮酸依赖性生物合成途径的实施，结合废除PHB生物合成和减少通过三羧酸循环的通量，能够设计菌株，产生2.97g/L的( R )-1， 3-BDO 并自养达到近 0.4 Cmol Cmol ^-1 h ^{-1 的}生产率。这是(R )-1,3-BDO 从 CO ₂生产。