PMID- 24525332
OWN - NLM
STAT- MEDLINE
DCOM- 20141216
LR  - 20220318
IS  - 1096-7184 (Electronic)
IS  - 1096-7176 (Linking)
VI  - 23
DP  - 2014 May
TI  - Metabolic engineering of a Saccharomyces cerevisiae strain capable of 
      simultaneously utilizing glucose and galactose to produce enantiopure 
      (2R,3R)-butanediol.
PG  - 92-9
LID - S1096-7176(14)00009-3 [pii]
LID - 10.1016/j.ymben.2014.02.003 [doi]
AB  - 2,3-Butanediol (BDO) is an important chemical with broad industrial applications 
      and can be naturally produced by many bacteria at high levels. However, the 
      pathogenicity of these native producers is a major obstacle for large scale 
      production. Here we report the engineering of an industrially friendly host, 
      Saccharomyces cerevisiae, to produce BDO at high titer and yield. By inactivation 
      of pyruvate decarboxylases (PDCs) followed by overexpression of MTH1 and adaptive 
      evolution, the resultant yeast grew on glucose as the sole carbon source with 
      ethanol production completely eliminated. Moreover, the pdc- strain consumed 
      glucose and galactose simultaneously, which to our knowledge is unprecedented in 
      S. cerevisiae strains. Subsequent introduction of a BDO biosynthetic pathway 
      consisting of the cytosolic acetolactate synthase (cytoILV2), Bacillus subtilis 
      acetolactate decarboxylase (BsAlsD), and the endogenous butanediol dehydrogenase 
      (BDH1) resulted in the production of enantiopure (2R,3R)-butanediol (R-BDO). In 
      shake flask fermentation, a yield over 70% of the theoretical value was achieved. 
      Using fed-batch fermentation, more than 100g/L R-BDO (1100mM) was synthesized 
      from a mixture of glucose and galactose, two major carbohydrate components in red 
      algae. The high titer and yield of the enantiopure R-BDO produced as well as the 
      ability to co-ferment glucose and galactose make our engineered yeast strain a 
      superior host for cost-effective production of bio-based BDO from renewable 
      resources.
CI  - Copyright (c) 2014 International Metabolic Engineering Society. Published by 
      Elsevier Inc. All rights reserved.
FAU - Lian, Jiazhang
AU  - Lian J
AD  - Department of Chemical and Biomolecular Engineering, University of Illinois at 
      Urbana-Champaign, Urbana, IL 61801, United States; Energy Biosciences Institute, 
      Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 
      Urbana, IL 61801, United States.
FAU - Chao, Ran
AU  - Chao R
AD  - Department of Chemical and Biomolecular Engineering, University of Illinois at 
      Urbana-Champaign, Urbana, IL 61801, United States; Energy Biosciences Institute, 
      Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 
      Urbana, IL 61801, United States.
FAU - Zhao, Huimin
AU  - Zhao H
AD  - Department of Chemical and Biomolecular Engineering, University of Illinois at 
      Urbana-Champaign, Urbana, IL 61801, United States; Energy Biosciences Institute, 
      Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 
      Urbana, IL 61801, United States; Departments of Chemistry, Biochemistry, and 
      Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, 
      United States. Electronic address: zhao5@illinois.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140210
PL  - Belgium
TA  - Metab Eng
JT  - Metabolic engineering
JID - 9815657
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Butylene Glycols)
RN  - 0 (MTH1 protein, S cerevisiae)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Sweetening Agents)
RN  - 45427ZB5IJ (2,3-butylene glycol)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.4 (butanediol dehydrogenase)
RN  - EC 2.2.1.6 (Acetolactate Synthase)
RN  - EC 4.1.1.- (Carboxy-Lyases)
RN  - EC 4.1.1.5 (acetolactate decarboxylase)
RN  - IY9XDZ35W2 (Glucose)
RN  - X2RN3Q8DNE (Galactose)
SB  - IM
MH  - Acetolactate Synthase/biosynthesis/genetics
MH  - Adaptor Proteins, Signal Transducing/genetics/metabolism
MH  - Alcohol Oxidoreductases/biosynthesis/genetics
MH  - Bacillus subtilis/enzymology/genetics
MH  - Bacterial Proteins/biosynthesis/genetics
MH  - Butylene Glycols/*metabolism
MH  - Carboxy-Lyases/biosynthesis/genetics
MH  - Directed Molecular Evolution/methods
MH  - Galactose/*metabolism/pharmacology
MH  - Glucose/*metabolism/pharmacology
MH  - Metabolic Engineering/*methods
MH  - Recombinant Proteins/biosynthesis/genetics
MH  - Saccharomyces cerevisiae/*genetics/*metabolism
MH  - Saccharomyces cerevisiae Proteins/genetics/metabolism
MH  - Sweetening Agents/metabolism/pharmacology
OTO - NOTNLM
OT  - (2R,3R)-Butanediol
OT  - Glucose derepression
OT  - Metabolic engineering
OT  - Pyruvate decarboxylase
OT  - Sugar co-utilization
EDAT- 2014/02/15 06:00
MHDA- 2014/12/17 06:00
CRDT- 2014/02/15 06:00
PHST- 2013/06/25 00:00 [received]
PHST- 2014/01/21 00:00 [revised]
PHST- 2014/02/03 00:00 [accepted]
PHST- 2014/02/15 06:00 [entrez]
PHST- 2014/02/15 06:00 [pubmed]
PHST- 2014/12/17 06:00 [medline]
AID - S1096-7176(14)00009-3 [pii]
AID - 10.1016/j.ymben.2014.02.003 [doi]
PST - ppublish
SO  - Metab Eng. 2014 May;23:92-9. doi: 10.1016/j.ymben.2014.02.003. Epub 2014 Feb 10.