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Enhancement of acetoin production in Candida glabrata by in silico-aided metabolic engineering.
- Source :
-
Microbial cell factories [Microb Cell Fact] 2014 Apr 13; Vol. 13 (1), pp. 55. Date of Electronic Publication: 2014 Apr 13. - Publication Year :
- 2014
-
Abstract
- Background: Acetoin is a promising chemical compound that can potentially serve as a high value-added platform for a broad range of applications. Many industrial biotechnological processes are moving towards the use of yeast as a platform. The multi-auxotrophic yeast, Candida glabrata, can accumulate a large amount of pyruvate, but produces only trace amounts of acetoin. Here, we attempted to engineer C. glabrata to redirect the carbon flux of pyruvate to increase acetoin production.<br />Results: Based on an in silico strategy, a synthetic, composite metabolic pathway involving two distinct enzymes, acetolactate synthase (ALS) and acetolactate decarboxylase (ALDC), was constructed, leading to the accumulation of acetoin in C. glabrata. Further genetic modifications were introduced to increase the carbon flux of the heterologous pathway, increasing the production of acetoin to 2.08 g/L. Additionally, nicotinic acid was employed to regulate the intracellular NADH level, and a higher production of acetoin (3.67 g/L) was obtained at the expense of 2,3-butanediol production under conditions of a lower NADH/NAD+ ratio.<br />Conclusion: With the aid of in silico metabolic engineering and cofactor engineering, C. glabrata was designed and constructed to improve acetoin production.
- Subjects :
- Acetolactate Synthase genetics
Acetolactate Synthase metabolism
Butylene Glycols metabolism
Carbon metabolism
Carboxy-Lyases genetics
Carboxy-Lyases metabolism
Ethanol metabolism
Metabolic Networks and Pathways drug effects
NAD metabolism
Niacin pharmacology
Plasmids genetics
Plasmids metabolism
Promoter Regions, Genetic
Acetoin metabolism
Candida glabrata metabolism
Metabolic Engineering
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2859
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Microbial cell factories
- Publication Type :
- Academic Journal
- Accession number :
- 24725668
- Full Text :
- https://doi.org/10.1186/1475-2859-13-55