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

Gascoyne, Joshua Luke; Bommareddy, Rajesh Reddy; Heeb, Stephan; Malys, Naglis

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.

Citation

Gascoyne, J. L., Bommareddy, R. R., Heeb, S., & Malys, N. (2021). Engineering Cupriavidus necator H16 for the autotrophic production of (R)-1,3-butanediol. Metabolic Engineering, 67, 262-276. https://doi.org/10.1016/j.ymben.2021.06.010

• Journal Article Type: Article
• Acceptance Date: Jun 30, 2021
• Online Publication Date: Jul 2, 2021
• Publication Date: Sep 1, 2021
• Deposit Date: Jul 16, 2021
• Publicly Available Date: Jul 16, 2021
• Journal: Metabolic Engineering
• Print ISSN: 1096-7176
• Electronic ISSN: 1096-7184
• Publisher: Elsevier BV
• Peer Reviewed: Peer Reviewed
• Volume: 67
• Pages: 262-276
• DOI: https://doi.org/10.1016/j.ymben.2021.06.010
• Keywords: Applied Microbiology and Biotechnology; Bioengineering; Biotechnology
• Public URL: https://nottingham-repository.worktribe.com/output/5787244
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1096717621001099?via%3Dihub