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Regulation of thiamine synthesis in Saccharomyces cerevisiae for improved pyruvate production
Author(s) -
Xu Guoqiang,
Hua Qiang,
Duan Ningjun,
Liu Liming,
Chen Jian
Publication year - 2012
Publication title -
yeast
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.923
H-Index - 102
eISSN - 1097-0061
pISSN - 0749-503X
DOI - 10.1002/yea.2902
Subject(s) - thiamine , saccharomyces cerevisiae , pyruvate decarboxylase , fermentation , biochemistry , pyruvate carboxylase , biology , pyruvate decarboxylation , metabolic engineering , pyruvic acid , pyruvate dehydrogenase kinase , strain (injury) , yield (engineering) , ethanol , enzyme , yeast , alcohol dehydrogenase , metallurgy , materials science , anatomy
Metabolic engineering of Saccharomyces cerevisiae for high‐yield production of carboxylic acid requires a cytosolic pyruvate pool as precursor. In this study, a novel strategy to improve pyruvate production and reduce metabolic by‐products via regulating thiamine synthesis was explored. Two of the thiamine biosynthesis regulatory genes, THI2 and THI3 , were disrupted in the S. cerevisiae parent strain FMME‐002. The mutants FMME‐002 ΔTHI2 and FMME‐002 ΔTHI3 both exhibited an enhanced pyruvate yield. Moreover, FMME‐002 ΔTHI2 achieved a relatively higher pyruvate production, and the highest concentration of pyruvate was achieved when 0.04 µ m thiamine was added. Enzyme assays and fermentation profiles of the THI2 ‐complemented strain indicated that the observed metabolic changes represented intrinsic effects of THI2 deletion on the physiology of S. cerevisiae . Under optimal C:N ratio conditions, FMME‐002 ΔTHI2 produced pyruvate up to 8.21 ± 0.30 g/l, whereas the ethanol titre decreased to 2.21 ± 0.24 g/l after 96 h of cultivation. These results demonstrate the possibility of improving pyruvate production by regulating thiamine synthesis in S. cerevisiae . Copyright © 2012 John Wiley & Sons, Ltd.