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Protein Engineering of Coenzyme‐A‐Dependent Aldehyde Dehydrogenase for Commercial Scale 1,4‐Butanediol Production in Escherichia coli
Author(s) -
Shah Amit,
Liu Wayne,
Kinley Brian,
Kuchinskas Mike,
Chan Kui,
Steer Brian,
Li Jingyi,
Yim Harry
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.720.4
Subject(s) - metabolic engineering , cofactor , biochemistry , chemistry , heterologous , flux (metallurgy) , protein engineering , escherichia coli , substrate (aquarium) , enzyme , aldehyde dehydrogenase , alcohol dehydrogenase , fermentation , dehydrogenase , biocatalysis , biology , organic chemistry , catalysis , gene , reaction mechanism , ecology
Genomatica has developed a novel commercial process, the GENO BDO™ process, for direct production of the intermediate 1,4‐butanediol (BDO) from carbohydrate feedstocks. BDO is used in a variety of polymer applications, including polyurethanes and polyesters, with over 1.7 million tons of BDO produced annually. Genomatica has leveraged its integrated metabolic engineering platform to maximize carbon flux through the BDO synthetic pathway. This heterologous pathway includes a coenzyme‐A‐dependent aldehyde dehydrogenase (Ald), which catalyzes the conversion of 4‐hydroxybutryl‐CoA to 4‐hydroxybutyraldehyde in the presence of reduced cofactor. Genomatica has performed extensive protein engineering on this enzyme to develop an Ald biocatalyst with increased substrate specificity that can support the required high flux over the course of the entire fermentation. In this poster, the biochemical characteristics of the Ald variants and their impact on performance will be highlighted.