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Metabolic engineering of non-pathogenic microorganisms for 2,3-butanediol production

Abstract

2,3-Butanediol (2,3-BDO) is a promising commodity chemical with various industrial applications. While petroleum-based chemical processes currently dominate the industrial production of 2,3-BDO, fermentation-based production of 2,3-BDO provides an attractive alternative to chemical-based processes with regards to economic and environmental sustainability. The achievement of high 2,3-BDO titer, yield, and productivity in microbial fermentation is a prerequisite for the production of 2,3-BDO at large scales. Also, enantiopure production of 2,3-BDO production is desirable because 2,3-BDO stereoisomers have unique physicochemical properties. Pursuant to these goals, many metabolic engineering strategies to improve 2,3-BDO production from inexpensive sugars by Klebsiella oxytoca, Bacillus species, and Saccharomyces cerevisiae have been developed. This review summarizes the recent advances in metabolic engineering of non-pathogenic microorganisms to enable efficient and enantiopure production of 2,3-BDO.

Key points

K. oxytoca, Bacillus species, and S. cerevisiae have been engineered to achieve efficient 2,3-BDO production.

• Metabolic engineering of non-pathogenic microorganisms enabled enantiopure production of 2,3-BDO.

• Cost-effective 2,3-BDO production can be feasible by using renewable biomass.

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Abbreviations

2,3-BDO:

2,3-butanediol

BDH:

2,3-butanediol dehydrogenase

ALS:

α-acetolactate synthase

ALDC:

α-acetolactate decarboxylase

DAR:

diacetyl reductase

FBA:

flux balance analysis

PFL:

pyruvate formate-lyase

PDH:

pyruvate dehydrogenase

FDH:

formate dehydrogenase

Vc :

vitamin C

ADH:

alcohol dehydrogenase

Adh :

ADH-deficient

Pdc :

PDC-deficient

ALE:

adaptive laboratory evolution

DHAP:

dihydroxyacetone phosphate

G3P:

glycerol-3-phosphate

PEPC:

phosphoenolpyruvate carboxylase

MDH:

malate dehydrogenase

FH:

fumarase

FRD:

fumarate reductase

LDH:

lactate dehydrogenase

ALD:

aldehyde dehydrogenase

PTA:

phosphate acetyltransferase

ACK:

acetate kinase

AR:

aldose reductase

TPI:

triose phosphate isomerase

GPDH:

glycerol-3-phosphate dehydrogenase

SSF:

simultaneous saccharification and fermentation

XR:

xylose reductase

XDH:

xylitol dehydrogenase

XK:

xylulose kinase

TEA:

techno-economic assessment

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Funding

This work is supported by the DOE Center for Advanced Bioenergy and Bioproducts Innovation (U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research under Award Number DE-SC0018420). Any opinions, findings and conclusions or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the U.S. Department of Energy.

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Contributions

J.W.L reviewed the literature and wrote the manuscript. Y.-G.L and Y.-S.J. critically read, revised, and improved the manuscript. C.V.R. conceived the idea, reviewed, and supervised the study. All authors read and approved the manuscript.

Corresponding author

Correspondence to Christopher V. Rao.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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The authors declare no competing interests.

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Lee, J.W., Lee, YG., Jin, YS. et al. Metabolic engineering of non-pathogenic microorganisms for 2,3-butanediol production. Appl Microbiol Biotechnol 105, 5751–5767 (2021). https://doi.org/10.1007/s00253-021-11436-2

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  • DOI: https://doi.org/10.1007/s00253-021-11436-2

Keywords

  • 2,3-Butanediol (2,3-BDO)
  • Klebsiella oxytoca
  • Bacillus species
  • Saccharomyces cerevisiae
  • 2,3-BDO stereoisomers