Enhancement of acetoin production in Candida glabrata by in silico-aided metabolic engineering

Microbial Cell Factories

Research

Jian Chen¹  Liming Liu²  Xiang Gao²  Nan Xu²  Shubo Li² 

[1] State Key Laboratory of Food Science and Technology, Jiangnan University, 214122, Wuxi, Jiangsu, China;The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 214122, Wuxi, Jiangsu, China;State Key Laboratory of Food Science and Technology, Jiangnan University, 214122, Wuxi, Jiangsu, China;The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 214122, Wuxi, Jiangsu, China;Laboratory of Food Microbial-Manufacturing Engineering, Jiangnan University, 214122, Wuxi, China;

关键词: Acetoin;    Candida glabrata;    Cofactor engineering;    Heterologous pathway;    In silico;    Metabolic engineering;   

DOI  :  10.1186/1475-2859-13-55

 received in 2013-12-24, accepted in 2014-04-06,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundAcetoin 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.ResultsBased 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.ConclusionWith the aid of in silico metabolic engineering and cofactor engineering, C. glabrata was designed and constructed to improve acetoin production.

【 授权许可】

Unknown   
© Li et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.