title: Biotin-independent strains of Escherichia coli for enhanced streptavidin production.
abstract: Biotin is an archetypal vitamin used as cofactor for carboxylation reactions found in all forms of life. However, biotin biosynthesis is an elaborate multi-enzymatic process and metabolically costly. Moreover, many industrially relevant organisms are incapable of biotin synthesis resulting in the requirement to supplement defined media. Here we describe the creation of biotin-independent strains of Escherichia coli and Corynebacterium glutamicum through installation of an optimized malonyl-CoA bypass, which re-routes natural fatty acid synthesis, rendering the previously essential vitamin completely obsolete. We utilize biotin-independent E. coli for the production of the high-value protein streptavidin which was hitherto restricted because of toxic effects due to biotin depletion. The engineered strain revealed significantly improved streptavidin production resulting in the highest titers and productivities reported for this protein to date.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland. Electronic address: markus.jeschek@bsse.ethz.ch.
authors.forename: Markus
authors.initials: M
authors.lastname: Jeschek
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.
authors.forename: Maximilian O
authors.initials: MO
authors.lastname: Bahls
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.
authors.forename: Veronika
authors.initials: V
authors.lastname: Schneider
authors.affiliation: ISSB, Génopole Genavenir 6, Equipe Xénome, 91030 Evry Cedex, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Marlière
authors.affiliation: Department of Chemistry, University of Basel, Basel 4056, Switzerland. Electronic address: thomas.ward@unibas.ch.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ward
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland. Electronic address: sven.panke@bsse.ethz.ch.
authors.forename: Sven
authors.initials: S
authors.lastname: Panke
mesh_terms: D053898:Biosynthetic Pathways / Q000502:physiology; D001710:Biotin / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D024861:Genetic Enhancement / Q000379:methods*; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000502:physiology; D019809:Streptavidin / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D029968:Escherichia coli Proteins; D001710:Biotin; D019809:Streptavidin
keywords: Bioprocess; Biotin-independent; Escherichia coli; Streptavidin production