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Two-dimensional isobutyl acetate production pathways to improve carbon yield.

Tashiro Y, Desai SH, Atsumi S - Nat Commun (2015)

Bottom Line: To avoid these problems, we describe here the construction of a metabolic pathway that simultaneously utilizes glucose and acetate.We demonstrate the utility of this approach for isobutyl acetate (IBA) production, wherein IBA production with glucose and acetate achieves a higher carbon yield than with either sole carbon source.These results highlight the potential for this multiple carbon source approach to improve the TMCY and balance redox in biosynthetic pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, USA.

ABSTRACT
For an economically competitive biological process, achieving high carbon yield of a target chemical is crucial. In biochemical production, pyruvate and acetyl-CoA are primary building blocks. When sugar is used as the sole biosynthetic substrate, acetyl-CoA is commonly generated by pyruvate decarboxylation. However, pyruvate decarboxylation during acetyl-CoA formation limits the theoretical maximum carbon yield (TMCY) by releasing carbon, and in some cases also leads to redox imbalance. To avoid these problems, we describe here the construction of a metabolic pathway that simultaneously utilizes glucose and acetate. Acetate is utilized to produce acetyl-CoA without carbon loss or redox imbalance. We demonstrate the utility of this approach for isobutyl acetate (IBA) production, wherein IBA production with glucose and acetate achieves a higher carbon yield than with either sole carbon source. These results highlight the potential for this multiple carbon source approach to improve the TMCY and balance redox in biosynthetic pathways.

No MeSH data available.


Related in: MedlinePlus

Pathway design for IBA synthesis.(a) IBA pathway from glucose and acetate. (b) Acetate-assimilating pathways from E. coli. Ace, acetate; acetyl-P, acetyl phosphate; AdhA, alcohol dehydrogenase from L. lactis; AlsS, acetolactate synthase from Bacillus subtilis; ATF1, alcohol-O-acetyl transferase from Saccharomyces cerevisiae; Glu, D-glucose; IBA; isobutyl acetate; IlvC, 2-hydroxy-3-ketol-acid reductoisomerase from E. coli; IlvD, dihydroxy-acid hydratase from E. coli; Kivd, 2-keto acid decarboxylase from Lactococcus lactis.
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f1: Pathway design for IBA synthesis.(a) IBA pathway from glucose and acetate. (b) Acetate-assimilating pathways from E. coli. Ace, acetate; acetyl-P, acetyl phosphate; AdhA, alcohol dehydrogenase from L. lactis; AlsS, acetolactate synthase from Bacillus subtilis; ATF1, alcohol-O-acetyl transferase from Saccharomyces cerevisiae; Glu, D-glucose; IBA; isobutyl acetate; IlvC, 2-hydroxy-3-ketol-acid reductoisomerase from E. coli; IlvD, dihydroxy-acid hydratase from E. coli; Kivd, 2-keto acid decarboxylase from Lactococcus lactis.

Mentions: Another method to improve the TMCY is to avoid decarboxylation. In cellular metabolism, acetyl-CoA is a building block for various metabolites such as amino acids, lipids and alcohols21. When sugars (that is, glucose) are used as starting substrates, acetyl-CoA is generated from pyruvate with carbon loss (Fig. 1a)22, reducing the TMCY in an acetyl-CoA-dependent pathway23. If acetyl-CoA can be generated without carbon loss, the TMCY would be enhanced for every acetyl-CoA-dependent pathway. Non-oxidative glycolysis (NOG) has been developed to produce acetyl-CoA from sugars without losing carbon23. Carbon yield from acetate as a substrate via the NOG reached 88% versus 67% via glycolysis. This work demonstrated that avoiding pyruvate decarboxylation is a useful approach to improve carbon yield. However, the NOG does not generate redox energy and therefore it is not directly applicable for production of high potential energy compounds such as alcohols or esters that depend on redox energy for their synthesis.


Two-dimensional isobutyl acetate production pathways to improve carbon yield.

Tashiro Y, Desai SH, Atsumi S - Nat Commun (2015)

Pathway design for IBA synthesis.(a) IBA pathway from glucose and acetate. (b) Acetate-assimilating pathways from E. coli. Ace, acetate; acetyl-P, acetyl phosphate; AdhA, alcohol dehydrogenase from L. lactis; AlsS, acetolactate synthase from Bacillus subtilis; ATF1, alcohol-O-acetyl transferase from Saccharomyces cerevisiae; Glu, D-glucose; IBA; isobutyl acetate; IlvC, 2-hydroxy-3-ketol-acid reductoisomerase from E. coli; IlvD, dihydroxy-acid hydratase from E. coli; Kivd, 2-keto acid decarboxylase from Lactococcus lactis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4491173&req=5

f1: Pathway design for IBA synthesis.(a) IBA pathway from glucose and acetate. (b) Acetate-assimilating pathways from E. coli. Ace, acetate; acetyl-P, acetyl phosphate; AdhA, alcohol dehydrogenase from L. lactis; AlsS, acetolactate synthase from Bacillus subtilis; ATF1, alcohol-O-acetyl transferase from Saccharomyces cerevisiae; Glu, D-glucose; IBA; isobutyl acetate; IlvC, 2-hydroxy-3-ketol-acid reductoisomerase from E. coli; IlvD, dihydroxy-acid hydratase from E. coli; Kivd, 2-keto acid decarboxylase from Lactococcus lactis.
Mentions: Another method to improve the TMCY is to avoid decarboxylation. In cellular metabolism, acetyl-CoA is a building block for various metabolites such as amino acids, lipids and alcohols21. When sugars (that is, glucose) are used as starting substrates, acetyl-CoA is generated from pyruvate with carbon loss (Fig. 1a)22, reducing the TMCY in an acetyl-CoA-dependent pathway23. If acetyl-CoA can be generated without carbon loss, the TMCY would be enhanced for every acetyl-CoA-dependent pathway. Non-oxidative glycolysis (NOG) has been developed to produce acetyl-CoA from sugars without losing carbon23. Carbon yield from acetate as a substrate via the NOG reached 88% versus 67% via glycolysis. This work demonstrated that avoiding pyruvate decarboxylation is a useful approach to improve carbon yield. However, the NOG does not generate redox energy and therefore it is not directly applicable for production of high potential energy compounds such as alcohols or esters that depend on redox energy for their synthesis.

Bottom Line: To avoid these problems, we describe here the construction of a metabolic pathway that simultaneously utilizes glucose and acetate.We demonstrate the utility of this approach for isobutyl acetate (IBA) production, wherein IBA production with glucose and acetate achieves a higher carbon yield than with either sole carbon source.These results highlight the potential for this multiple carbon source approach to improve the TMCY and balance redox in biosynthetic pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, USA.

ABSTRACT
For an economically competitive biological process, achieving high carbon yield of a target chemical is crucial. In biochemical production, pyruvate and acetyl-CoA are primary building blocks. When sugar is used as the sole biosynthetic substrate, acetyl-CoA is commonly generated by pyruvate decarboxylation. However, pyruvate decarboxylation during acetyl-CoA formation limits the theoretical maximum carbon yield (TMCY) by releasing carbon, and in some cases also leads to redox imbalance. To avoid these problems, we describe here the construction of a metabolic pathway that simultaneously utilizes glucose and acetate. Acetate is utilized to produce acetyl-CoA without carbon loss or redox imbalance. We demonstrate the utility of this approach for isobutyl acetate (IBA) production, wherein IBA production with glucose and acetate achieves a higher carbon yield than with either sole carbon source. These results highlight the potential for this multiple carbon source approach to improve the TMCY and balance redox in biosynthetic pathways.

No MeSH data available.


Related in: MedlinePlus