Efficient hydroxyproline production from glucose in minimal media by <i>Corynebacterium glutamicum</i>

Falcioni, Francesco; Bühler, Bruno; Schmid, Andreas

doi:10.1002/bit.25442

Cited by 30 publications

(27 citation statements)

References 42 publications

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“…Thet argeted deletion of degrading pathways [13] or an optimization of the reaction conditions (as reported here for 6a)c an be used to circumvent this challenge. Furthermore,i ti sf requently observed in wholecell biotransformations that the fed substrates and products are metabolized by the cellular metabolism.…”

Section: Angewandte Chemiementioning

confidence: 99%

Recombinant Cyanobacteria for the Asymmetric Reduction of C=C Bonds Fueled by the Biocatalytic Oxidation of Water

et al. 2016

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A recombinant enoate reductase was expressed in cyanobacteria and used for the light-catalyzed, enantioselective reduction of C=C bonds. The coupling of oxidoreductases to natural photosynthesis allows asymmetric syntheses fueled by the oxidation of water. Bypassing the addition of sacrificial cosubstrates as electron donors significantly improves the atom efficiency and avoids the formation of undesired side products. Crucial factors for product formation are the availability of NADPH and the amount of active enzyme in the cells. The efficiency of the reaction is comparable to typical whole-cell biotransformations in E. coli. Under optimized conditions, a solution of 100 mg prochiral 2-methylmaleimide was reduced to optically pure 2-methylsuccinimide (99 % ee, 80 % yield of isolated product). High product yields and excellent optical purities demonstrate the synthetic usefulness of light-catalyzed whole-cell biotransformations using recombinant cyanobacteria.

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Section: Angewandte Chemiementioning

confidence: 99%

Recombinant Cyanobacteria for the Asymmetric Reduction of C=C Bonds Fueled by the Biocatalytic Oxidation of Water

et al. 2016

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“…The previous study indicated that an insufficient supply of DO is an important issue in Hyp fermentation, as it leads to low Hyp yield and the accumulation of acetic acid [11][12][13][14]. Zhao et al [10].…”

Section: Effect Of the Added-protease Fermentation On Hyp Productionmentioning

confidence: 99%

“…In addition, the rate of glucose conversion to Hyp in the APF was 18.1%, while that in CF was 16.7%, which was an increase of 8.4%. Acetic acid is the main metabolic by-product of Hyp production in E. coli, which is generated by metabolic overflow when the oxygen supply is limited [14]. The acetic acid production rate in the APF was obviously lower than that in CF at 18-38 h, and the final concentrations in CF and APF were 4.8 g/L and 2.3 g/L, respectively, which was a decrease of 52.1%, suggesting improvement of oxygen transfer.…”

Section: Effect Of the Added-protease Fermentation On Hyp Productionmentioning

confidence: 99%

“…The accumulation of acetate is inversely correlated with DO levels, and acetate accumulation can be reduced by maintaining high DO levels at stationary growth phase [12,13]. Therefore, oxygen supply is generally considered to be a major limiting factor in Hyp production by recombinant strains [14]. At present, there are two strategies for solving the problem of insufficient oxygen supply during high-density fermentation.…”

Section: Introductionmentioning

confidence: 99%

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Hydrolysing the soluble protein secreted by Escherichia coli in trans-4-hydroxy-L-proline fermentation increased dissolve oxygen to promote high-level trans-4-hydroxy-L-proline production

Liu

2019

Bioengineered

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Trans-4-hydroxy-L-proline (Hyp) production by Escherichia coli (E. coli) in fermentation is a highoxygen-demand process. E. coli secretes large amounts of soluble protein, especially in the anaphase of fermentation, which is an important factor leading to inadequate oxygen supply. And acetic acid that is the major by-product of Hyp production accumulates under low dissolved oxygen (DO). To increase DO and achieve high-level Hyp production, soluble protein was hydrolysed by adding protease in Hyp fermentation. The optimal protease, concentration, and addition time were trypsin, 0.2 g/L, and 18 h, respectively. With the addition of trypsin, the soluble protein in Hyp fermentation decreased by 43.5%. The DO could be maintained at 20-30% throughout fermentation. Hyp production and glucose conversion rate were 45.3 g/L and 18.1%, which were increases of 24.1% and 8.4%, respectively. The accumulation of acetic acid was decreased by 52.1%. The metabolic flux of Hyp was increased by 44.2% and the flux of acetate was decreased by 51.0%. ARTICLE HISTORY

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“…When the codon-optimized p4h gene was heterogeneously expressed in four C. glutamicum strains, Hyp production was relatively low (<0.12 g/L; Yi et al, 2014). An isoleucine bradytrophy C. glutamicum strain expressing the p4h gene produced 7.1 g/L of Hyp from glucose by limiting an external isoleucine supply in a fed-batch cultivation (Falcioni et al, 2015). In spite of the high production of L-proline in C. glutamicum (Y.…”

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confidence: 99%

Reconstruction of tricarboxylic acid cycle in Corynebacterium glutamicum with a genome‐scale metabolic network model for trans‐4‐hydroxyproline production

Zhang

Shang

Wang

et al. 2018

Biotech & Bioengineering

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trans-4-Hydroxy- l-proline (Hyp) is an abundant component of mammalian collagen and functions as a chiral synthon for the syntheses of anti-inflammatory drugs in the pharmaceutical industry. Proline 4-hydroxylase (P4H) can catalyze the conversion of l-proline to Hyp; however, it is still challenging for the fermentative production of Hyp from glucose using P4H due to the low yield and productivity. Here, we report the metabolic engineering of Corynebacterium glutamicum for the fermentative production of Hyp by reconstructing tricarboxylic acid (TCA) cycle together with heterologously expressing the p4h gene from Dactylosporangium sp. strain RH1. In silico model-based simulation showed that α-ketoglutarate was redirected from the TCA cycle toward Hyp synthetic pathway driven by P4H when the carbon flux from succinyl-CoA to succinate descended to zero. The interruption of the TCA cycle by the deletion of sucCD-encoding the succinyl-CoA synthetase (SUCOAS) led to a 60% increase in Hyp production and had no obvious impact on the growth rate. Fine-tuning of plasmid-borne ProB* and P4H abundances led to a significant increase in the yield of Hyp on glucose. The final engineered Hyp-7 strain produced up to 21.72 g/L Hyp with a yield of 0.27 mol/mol (Hyp/glucose) and a volumetric productivity of 0.36 g·L ·hr in the shake flask fermentation. To our knowledge, this is the highest yield and productivity achieved by microbial fermentation in a glucose-minimal medium for Hyp production. This strategy provides new insights into engineering C. glutamicum by flux coupling for the fermentative production of Hyp and related products.

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Efficient hydroxyproline production from glucose in minimal media by Corynebacterium glutamicum

Cited by 30 publications

References 42 publications

Recombinant Cyanobacteria for the Asymmetric Reduction of C=C Bonds Fueled by the Biocatalytic Oxidation of Water

Recombinant Cyanobacteria for the Asymmetric Reduction of C=C Bonds Fueled by the Biocatalytic Oxidation of Water

Hydrolysing the soluble protein secreted by Escherichia coli in trans-4-hydroxy-L-proline fermentation increased dissolve oxygen to promote high-level trans-4-hydroxy-L-proline production

Reconstruction of tricarboxylic acid cycle in Corynebacterium glutamicum with a genome‐scale metabolic network model for trans‐4‐hydroxyproline production

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