Abstract
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.
Highlights
Butanediols are widely used in the synthesis of polymers, specialty chemicals and important chemical in termediates
The systematic approach to engineer C. necator H16 for 1,3-BDO production was based on the following design and experimental ratio nale: 1) considering alternative biosynthetic pathways which enable to utilise pyruvate and its downstream anabolic products as precursors; 2) screening enzymes with butanal dehydrogenase and aldehyde reductase activities enabling biosynthesis of 1,3-BDO from (R)-3-hydroxybutyr aldehyde-CoA, the natural pyruvate’s anabolic product in C. necator; 3) engineering C. necator H16 strain to improve the flux towards precursors required for 1,3-BDO biosynthesis; 4) establishing fermentation condi tions and strain engineering to reduce the by-product biosynthesis; 5) developing C. necator H16 strain suitable for production 1,3BDO from CO2
The (R)-1,3-BDO biosynthesis was achieved by heterologous gene expression of either C. saccharoperbutylacetonicum bld in combi nation with E. coli yqhD or C. acetobutylicum adhE2
Summary
Butanediols are widely used in the synthesis of polymers, specialty chemicals and important chemical in termediates. Imple mentation 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. Application of this pathway, consisting of pyruvate decarbox ylase (PDC) from Zimomonas mobilis, deoxyribose-5-phosphate aldolase (Dra) from Bacillus halodurans and aldo/keto reductase (AKR) from Pseudomonas aeruginosa, has resulted in 2.4 g/L of 1,3-BDO with the yield of 56 mg/g glucose (Nemr et al, 2018)
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