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Precursor Balancing for Metabolic Engineering of Lycopene Production in Escherichia coli
Author(s) -
Farmer William R.,
Liao James C.
Publication year - 2001
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1021/bp000137t
Subject(s) - lycopene , metabolic engineering , metabolic flux analysis , flux (metallurgy) , escherichia coli , biochemistry , metabolism , metabolic pathway , chemistry , biosynthesis , biology , carotenoid , enzyme , gene , organic chemistry
One issue that must be addressed in the rational design of metabolic pathways is the elimination of potential bottlenecks in the upstream pathways. We have reconstructed the isoprenoid pathway to overproduce the carotenoid lycopene in Escherichia coli . Here we show that the distribution between pyruvate and glyceraldehyde 3‐phosphate (G3P), the originating precursors of the isoprenoid pathway, is a major factor that can limit isoprenoid production yields in E. coli . In particular, alterations in the central metabolism that redirect flux from pyruvate back to G3P enhance lycopene production, while alterations that channel carbon flux away from the G3P pool have the opposite effect. These results suggest that G3P may be limiting in the biosynthesis of lycopene, and modifications that achieve a more equitable distribution between the two precursors are able to increase the lycopene yield in metabolically engineered E. coli .