Abstract：
:Succinic acid is a platform chemical of recognized industrial value and accordingly faces a continuous challenge to enable manufacturing from most attractive raw materials. It is mainly produced from glucose, using microbial fermentation. Here, we explore and optimize succinate production from sucrose, a globally applied substrate in biotechnology, using the rumen bacterium Basfia succiniciproducens DD1. As basis of the strain optimization, the yet unknown sucrose metabolism of the microbe was studied, using 13C metabolic flux analyses. When grown in batch culture on sucrose, the bacterium exhibited a high succinate yield of 1molmol-1 and a by-product spectrum, which did not match the expected PTS-mediated sucrose catabolism. This led to the discovery of a fructokinase, involved in sucrose catabolism. The flux approach unraveled that the fructokinase and the fructose PTS both contribute to phosphorylation of the fructose part of sucrose. The contribution of the fructokinase reduces the undesired loss of the succinate precursor PEP into pyruvate and into pyruvate-derived by-products and enables increased succinate production, exclusively via the reductive TCA cycle branch. These findings were used to design superior producers. Mutants, which (i) overexpress the beneficial fructokinase, (II) lack the competing fructose PTS, and (iii) combine both traits, produce significantly more succinate. In a fed-batch process, B. succiniciproducens ΔfruA achieved a titer of 71gL-1 succinate and a yield of 2.5molmol-1 from sucrose.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Lange A,Becker J,Schulze D,Cahoreau E,Portais JC,Haefner S,Schröder H,Krawczyk J,Zelder O,Wittmann Cdoi
10.1016/j.ymben.2017.10.003subject
Has Abstractpub_date
2017-11-01 00:00:00pages
198-212eissn
1096-7176issn
1096-7184pii
S1096-7176(17)30175-1journal_volume
44pub_type
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