Production of succinic acid at low pH by a recombinant strain of the aerobic yeast <i>Yarrowia lipolytica</i>

Yuzbashev, Tigran V.; Yuzbasheva, Evgeniya Y.; Sobolevskaya, Irina Nikolaevna; Laptev, Ivan A.; Vybornaya, Tatiana V.; Larina, Anna S.; Matsui, Kunihiko; Fukui, Keita; Sineoky, S. P.

doi:10.1002/bit.22859

Cited by 137 publications

(95 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Succinic acid is an important compound as a building block of useful chemicals (Cheng et al, 2012;Delhomme et al, 2009). Many studies on metabolic engineering of microorganisms for succinic acid production have been reported ( Okino et al, 2008;Thakker et al, 2012;Wang et al, 2011a, b;Wendisch et al, 2006;Wieschalka et al, 2013;Yuzbashev et al, 2010;Zhang et al, 2009Zhang et al, , 2010. From the viewpoint of metabolic engineering of C. glutamicum for succinic acid production, introduction of E. coli pntAB seems to be an effective way to enhance succinic acid production under microaerobic conditions.…”

Section: Discussionmentioning

confidence: 99%

Enhanced acetic acid and succinic acid production under microaerobic conditions by Corynebacterium glutamicum harboring Escherichia coli transhydrogenase gene pntAB

Yamauchi¹,

Hirasawa²,

Nishii³

et al. 2014

J. Gen. Appl. Microbiol.

View full text Add to dashboard Cite

Some microorganisms, such as Escherichia coli, harbor transhydrogenases that catalyze the interconversion between NADPH and NADH. However, such transhydrogenase genes have not been found in the genome of a glutamic acid-producing bacterium Corynebacterium glutamicum. In this study, the E. coli transhydrogenase genes udhA and pntAB were introduced into the C. glutamicum wild-type strain ATCC 13032, and the metabolic characteristics of the recombinant strains under aerobic and microaerobic conditions were examined. No major metabolic changes were observed following the introduction of the E. coli transhydrogenase genes under aerobic conditions. Under microaerobic conditions, significant metabolic change was not observed following the introduction of the udhA gene. However, the specific production rates of lactic acid, acetic acid, and succinic acid, and the overall production levels of acetic acid and succinic acid were increased by introducing the E. coli pntAB gene. Moreover, the NADH/NAD + ratio was increased by introduction of pntAB. Our results suggest that the E. coli PntAB transhydrogenase enhances the conversion of NADPH to NADH in C. glutamicum under microaerobic conditions, and the increased NADH/NAD + ratio results in increased succinic acid production. In addition, acetic acid production might be enhanced to supply ATP to the anaplerotic reaction catalyzed by pyruvate carboxylase.Key words: acetic acid; Corynebacterium glutamicum; pntAB; redox balance; succinic acid; transhydrogenases IntroductionMany oxidation and reduction reactions are involved in cellular metabolism, most of which require pyrimidine nucleotide cofactors, such as nicotinamide adenine dinucleotide (NAD + ) and nicotinamide adenine dinucleotide phosphate (NADP + ) and their reduced forms NADH and NADPH, to supply oxidizing and reducing equivalents. Generally, NADH is produced via catabolism, and is oxidized in the respiratory chain under aerobic conditions or by fermentation under anaerobic conditions. Anabolic reactions to produce cell biomass components, such as fatty acid and amino acid biosynthesis, require NADPH as a reducing equivalent. Therefore, maintaining the intracellular balance of NAD(P) + and NAD(P)H is very important for most intracellular metabolic reactions to occur.Some organisms contain the enzymes catalyzing the following interconversion of NADH and NADPH, called transhydrogenase:NADPH + NAD + NADP + + NADH. To date, two types of transhydrogenases have been identified; the cytoplasmic-soluble and membrane-bound types. Membrane-bound transhydrogenases have been found in the inner mitochondrial membrane of eukaryotic cells and in the cytoplasmic membrane of many bacteria, and simultaneously catalyze proton translocation across a membrane. Full PaperEnhanced acetic acid and succinic acid production under microaerobic conditions by Corynebacterium glutamicum harboring Escherichia coli transhydrogenase gene pntAB (Received April 3, 2014; Accepted April 8, 2014) Yuto Yamauchi, None of the authors of this manuscript ha...

show abstract

Section: Discussionmentioning

confidence: 99%

Enhanced acetic acid and succinic acid production under microaerobic conditions by Corynebacterium glutamicum harboring Escherichia coli transhydrogenase gene pntAB

Yamauchi¹,

Hirasawa²,

Nishii³

et al. 2014

J. Gen. Appl. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Up to 0.5 g succinic acid per gram of cells was detected for all tested Y. lipolytica strains. Additionally, succinic acid production was detected in both glycerol-(up to 5.1 g l −1 ) and glucose-containing media (up to 1.4 g l −1 ) (Kretschmar 2010;Yuzbashev et al 2010). Furthermore, first approaches for an increase in succinic acid production were presented in Kamzolova et al (2009b) and Yuzbashev et al (2010).…”

Section: Introductionmentioning

confidence: 97%

“…Although these microorganisms produce succinic acid efficiently, they have some disadvantages as some of them are obligate anaerobic and potentially pathogenic, or show poor growth and low tolerance to acid and osmotic stress (Song and Lee 2006). As a result, several research groups have focused their interest on processes with yeasts such as Saccharomyces cerevisiae or Yarrowia lipolytica to produce SA (Furukawa et al 1982;Kamzolova et al 2012aKamzolova et al , b, 2014aKamzolova and Morgunov 2013;Papanikolaou et al 2002;Raab et al 2010;Tsugawa et al 1969;Yuzbashev et al 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, succinic acid production was detected in both glycerol-(up to 5.1 g l −1 ) and glucose-containing media (up to 1.4 g l −1 ) (Kretschmar 2010;Yuzbashev et al 2010). Furthermore, first approaches for an increase in succinic acid production were presented in Kamzolova et al (2009b) and Yuzbashev et al (2010). In the latter case, a Y. lipolytica strain with mutations in genes encoding the succinate dehydrogenase (SDH) was constructed to achieve a reduction or loss of SDH enzyme activity.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The influence of oxygen limitation for the production of succinic acid with recombinant strains of Yarrowia lipolytica

Jost

Holz

Aurich

et al. 2014

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

The yeast Yarrowia lipolytica is able to produce high amounts of several organic acids such as pyruvic, citric, isocitric, alpha-ketoglutaric, and succinic acid. Here we report on the influence of the reduced activity of succinate dehydrogenase in Y. lipolytica on its ability to produce succinate. The recombinant strains Y. lipolytica H222-AZ1 and H222-AZ2 were created by exchange of the native promoter of the succinate dehydrogenase subunit 2 encoding gene by inducible promoters. During the cultivation of the strain Y. lipolytica H222-AZ1 in shaking flask experiments, it was found that the promoter exchange resulted in an increase in succinic acid (SA) production. Moreover, it was found that the production of SA depends on an additional limitation of oxygen. Fed-batch cultivations in 1-l bioreactors confirmed this fundamental finding. Y. lipolytica H222-AZ1 produced 2 g l(-1) of SA with oxygen supply and 9.2 g l(-1) under the limitation of oxygen after 165 h. By using a less active promoter in Y. lipolytica H222-AZ2, the production of SA was increased to 25 g l(-1) with a productivity of 0.152 g (l*h)(-1) and a selectivity of 67 % after 165 h. Yields of 2.39 g SA per gram biomass and 0.26 g SA per gram glycerol were found.

show abstract

“…On the other hand, similar to other ascomycetes, Y. lipolytica is considered to prefer an acidic pH media. Many strains of this species demonstrate an exclusive resistance to low pH (Yuzbashev et al, 2010). Taken together, these data show that the ambivalent pH adaptation molecular mechanisms in Y. lipolytica coupled to an extreme halotolerance, remains obscure.…”

Section: Introductionmentioning

confidence: 84%

Identification of Proteins Involved in pH Adaptation in Extremophile Yeast Yarrowia lipolytica

Epova¹,

Гусева²,

Kovalyov³

et al. 2012

Proteomic Applications in Biology

View full text Add to dashboard Cite

Production of succinic acid at low pH by a recombinant strain of the aerobic yeast Yarrowia lipolytica

Cited by 137 publications

References 34 publications

Enhanced acetic acid and succinic acid production under microaerobic conditions by Corynebacterium glutamicum harboring Escherichia coli transhydrogenase gene pntAB

Enhanced acetic acid and succinic acid production under microaerobic conditions by Corynebacterium glutamicum harboring Escherichia coli transhydrogenase gene pntAB

The influence of oxygen limitation for the production of succinic acid with recombinant strains of Yarrowia lipolytica

Identification of Proteins Involved in pH Adaptation in Extremophile Yeast Yarrowia lipolytica

Contact Info

Product

Resources

About