title: Combining metabolic engineering and biocompatible chemistry for high-yield production of homo-diacetyl and homo-(S,S)-2,3-butanediol.
abstract: Biocompatible chemistry is gaining increasing attention because of its potential within biotechnology for expanding the repertoire of biological transformations carried out by enzymes. Here we demonstrate how biocompatible chemistry can be used for synthesizing valuable compounds as well as for linking metabolic pathways to achieve redox balance and rescued growth. By comprehensive rerouting of metabolism, activation of respiration, and finally metal ion catalysis, we successfully managed to convert the homolactic bacterium Lactococcus lactis into a homo-diacetyl producer with high titer (95mM or 8.2g/L) and high yield (87% of the theoretical maximum). Subsequently, the pathway was extended to (S,S)-2,3-butanediol (S-BDO) through efficiently linking two metabolic pathways via chemical catalysis. This resulted in efficient homo-S-BDO production with a titer of 74mM (6.7g/L) S-BDO and a yield of 82%. The diacetyl and S-BDO production rates and yields obtained are the highest ever reported, demonstrating the promising combination of metabolic engineering and biocompatible chemistry as well as the great potential of L. lactis as a new production platform.
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Jianming
authors.initials: J
authors.lastname: Liu
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Siu Hung Joshua
authors.initials: SHJ
authors.lastname: Chan
authors.affiliation: Department of Chemistry, University of Copenhagen, University Park 5, Denmark.
authors.forename: Theis
authors.initials: T
authors.lastname: Brock-Nannestad
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Sang Yup
authors.initials: SY
authors.lastname: Lee
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark. Electronic address: chso@food.dtu.dk.
authors.forename: Christian
authors.initials: C
authors.lastname: Solem
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark. Electronic address: perj@food.dtu.dk.
authors.forename: Peter Ruhdal
authors.initials: PR
authors.lastname: Jensen
mesh_terms: D001672:Biocompatible Materials / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000502:physiology*; D002072:Butylene Glycols / Q000302:isolation & purification / Q000378:metabolism*; D024861:Genetic Enhancement / Q000379:methods*; D013294:Lactococcus lactis / Q000502:physiology*; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D002072:Butylene Glycols; D011994:Recombinant Proteins
keywords: Biocompatible chemistry; Homo-(S,S)-2,3-butanediol; Homo-diacetyl; Lactococcus lactis; Metabolic engineering