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Front Microbiol. 2015 Jun 25;6:632. doi: 10.3389/fmicb.2015.00632. eCollection 2015.

Reconstruction and in silico analysis of an Actinoplanes sp. SE50/110 genome-scale metabolic model for acarbose production.

Author information

1
Wuxi Medical School, Jiangnan University Wuxi, China ; State Key Laboratory of Food Science and Technology, Jiangnan University Wuxi, China ; Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University Wuxi, China.
2
State Key Laboratory of Food Science and Technology, Jiangnan University Wuxi, China ; Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University Wuxi, China.
3
Wuxi Medical School, Jiangnan University Wuxi, China ; Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University Wuxi, China.

Abstract

Actinoplanes sp. SE50/110 produces the α-glucosidase inhibitor acarbose, which is used to treat type 2 diabetes mellitus. To obtain a comprehensive understanding of its cellular metabolism, a genome-scale metabolic model of strain SE50/110, iYLW1028, was reconstructed on the bases of the genome annotation, biochemical databases, and extensive literature mining. Model iYLW1028 comprises 1028 genes, 1128 metabolites, and 1219 reactions. One hundred and twenty-two and eighty one genes were essential for cell growth on acarbose synthesis and sucrose media, respectively, and the acarbose biosynthetic pathway in SE50/110 was expounded completely. Based on model predictions, the addition of arginine and histidine to the media increased acarbose production by 78 and 59%, respectively. Additionally, dissolved oxygen has a great effect on acarbose production based on model predictions. Furthermore, genes to be overexpressed for the overproduction of acarbose were identified, and the deletion of treY eliminated the formation of by-product component C. Model iYLW1028 is a useful platform for optimizing and systems metabolic engineering for acarbose production in Actinoplanes sp. SE50/110.

KEYWORDS:

Actinoplanes sp. SE50/110; acarbose production; amino acids; genome-scale metabolic model; oxygen uptake rate

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