Combining rational metabolic engineering and flux optimization strategies for efficient production of fumaric acid

Content Provider	Semantic Scholar
Author	Song, Chan Woo Lee, Sang Yup
Copyright Year	2015
Abstract	Fumaric acid is an important C4-dicarboxylic acid widely used in chemical, food, and pharmaceutical industries. Rational metabolic engineering together with flux optimization were performed for the development of an Escherichia coli strain capable of efficiently producing fumaric acid. The initial engineered strain, CWF4N overexpressing phosphoenolpyruvate carboxylase (PPC), produced 5.30 g/L of fumaric acid. Optimization of PPC flux by examining 24 types of synthetic PPC expression vectors further increased the titer up to 5.72 g/L with a yield of 0.432 g/g·glucose. Overexpression of the succinate dehydrogenase complex (sdhCDAB) led to an increase in carbon yield up to 0.493 g/g·glucose. Based on this mutant strain, citrate synthase (CS) was combinatorially overexpressed and balanced with PPC using 48 types of synthetic expression vectors. As a result, 6.24 g/L of fumaric acid was produced with a yield of 0.500 g/g·glucose. Fed-batch culture of this final strain allowed production of 25.5 g/L of fumaric acid with a yield of 0.366 g/g·glucose. Deletion of the aspA gene encoding aspartase and supplementation of aspartic acid further increased the fumaric acid titer to 35.1 g/L with a yield of 0.490 g/g·glucose.
Starting Page	8455
Ending Page	8464
Page Count	10
File Format	PDF HTM / HTML
DOI	10.1007/s00253-015-6816-6
PubMed reference number	26194559
Journal	Medline
Volume Number	99
Alternate Webpage(s)	https://static-content.springer.com/esm/art:10.1007%2Fs00253-015-6816-6/MediaObjects/253_2015_6816_MOESM1_ESM.pdf
Alternate Webpage(s)	https://doi.org/10.1007/s00253-015-6816-6
Journal	Applied Microbiology and Biotechnology
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article