Open AccessSystems metabolic engineering of Escherichia coli for L ‐threonine production
Author(s) -
Lee Kwang Ho,
Park Jin Hwan,
Kim Tae Yong,
Kim Hyun Uk,
Lee Sang Yup
Publication year - 2007
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb4100196
Subject(s) - metabolic engineering , escherichia coli , biology , threonine , transcriptome , in silico , biochemistry , gene , bioproducts , synthetic biology , metabolic network , computational biology , microbiology and biotechnology , serine , gene expression , enzyme , biofuel
Amino‐acid producers have traditionally been developed by repeated random mutagenesis owing to the difficulty in rationally engineering the complex and highly regulated metabolic network. Here, we report the development of the genetically defined L ‐threonine overproducing Escherichia coli strain by systems metabolic engineering. Feedback inhibitions of aspartokinase I and III (encoded by thrA and lysC , respectively) and transcriptional attenuation regulations (located in thrL ) were removed. Pathways for Thr degradation were removed by deleting tdh and mutating ilvA . The metA and lysA genes were deleted to make more precursors available for Thr biosynthesis. Further target genes to be engineered were identified by transcriptome profiling combined with in silico flux response analysis, and their expression levels were manipulated accordingly. The final engineered E. coli strain was able to produce Thr with a high yield of 0.393 g per gram of glucose, and 82.4 g/l Thr by fed‐batch culture. The systems metabolic engineering strategy reported here may be broadly employed for developing genetically defined organisms for the efficient production of various bioproducts.