Engineering Cupriavidus necator H16 for the autotrophic production of (R)-1,3-butanediol

Gascoyne, Joshua Luke, Bommareddy, Rajesh Reddy, Heeb, Stephan and Malys, Naglis (2021) Engineering Cupriavidus necator H16 for the autotrophic production of (R)-1,3-butanediol. Metabolic Engineering, 67. pp. 262-276. ISSN 1096-7176

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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.

Item Type: Article
Additional Information: Funding Information: This work was supported by the Biotechnology and Biological Sciences Research Council [grant number BB/L013940/1 ] (BBSRC); and the Engineering and Physical Sciences Research Council (EPSRC) under the same grant number. We thank University of Nottingham for providing SBRC-DTProg PhD studentship to J.L.G.; Matthew Abbott and James Fothergill for assistance with HPLC analysis; Rebekka Biedendieck for gifting genomic DNA of B. megaterium; Erik Hanko for valuable discussions and assistance; and all members of SBRC who helped in carrying out this research.
Uncontrolled Keywords: 1,3-Butanediol, 4-Hydroxy-2-butanone, Metabolic engineering, Carbon dioxide, Autotrophic fermentation, Cupriavidus necator H16
Subjects: H800 Chemical, Process and Energy Engineering
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: John Coen
Date Deposited: 09 Jul 2021 13:05
Last Modified: 11 Aug 2021 14:15

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