title: Integrating biocompatible chemistry and manipulating cofactor partitioning in metabolically engineered Lactococcus lactis for fermentative production of (3S)-acetoin.
abstract: Biocompatible chemistry (BC), that is, non-enzymatic chemical reactions compatible with living organisms, is increasingly used in conjunction with metabolically engineered microorganisms for producing compounds that do not usually occur naturally. Here we report production of one such compound, (3S)-acetoin, a valuable precursor for chiral synthesis, using a metabolically engineered Lactococcus lactis strain growing under respiratory conditions with ferric iron serving as a BC component. The strain used has all competing product pathways inactivated, and an appropriate cofactor balance is achieved by fine-tuning the respiratory capacity indirectly via the hemin concentration. We achieve high-level (3S)-acetoin production with a final titer of 66 mM (5.8 g/L) and a high yield (71% of the theoretical maximum). To the best of our knowledge, this is the first report describing production of (3S)-acetoin from sugar by microbial fermentation, and the results obtained confirm the potential that lies with BC for producing useful chemicals. Biotechnol. Bioeng. 2016;113: 2744-2748. © 2016 Wiley Periodicals, Inc.
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800, Kgs. Lyngby, Denmark.
authors.forename: Jianming
authors.initials: J
authors.lastname: Liu
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800, Kgs. Lyngby, Denmark. chso@food.dtu.dk.
authors.forename: Christian
authors.initials: C
authors.lastname: Solem
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800, Kgs. Lyngby, Denmark. perj@food.dtu.dk.
authors.forename: Peter Ruhdal
authors.initials: PR
authors.lastname: Jensen
mesh_terms: D000093:Acetoin / Q000302:isolation & purification / Q000378:metabolism*; D003067:Coenzymes / Q000235:genetics / Q000378:metabolism; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D003198:Computer Simulation; D005285:Fermentation / Q000502:physiology; D024861:Genetic Enhancement / Q000379:methods; D005947:Glucose / Q000378:metabolism*; D013294:Lactococcus lactis / Q000502:physiology*; D060847:Metabolic Engineering / Q000379:methods*; D064688:Metabolic Flux Analysis / Q000379:methods; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D018511:Systems Integration
chemical_list: D003067:Coenzymes; D009097:Multienzyme Complexes; D000093:Acetoin; D005947:Glucose
keywords: (3S)-acetoin; biocompatible chemistry; cofactor partitioning; metabolic engineering