Cofactor engineering for advancing chemical biotechnology

Wang, Yipeng; San, Ka‐Yiu; Bennett, George N.

doi:10.1016/j.copbio.2013.03.022

Cited by 138 publications

(74 citation statements)

References 59 publications

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“…the manipulation of cofactor levels, as exemplified by SAM in this work, in addition to providing means to study cellular metabolism has the potential to be used as an additional tool to achieve desired metabolic engineering goals and fits with current trends in systems biotechnology. Our findings confirm the potential of cofactor-engineering strategies for industrial application [63]. Summarizing, at least four are the most relevant observations deriving from the current work.…”

Section: Discussionsupporting

confidence: 72%

Changes in SAM 2 expression affect lactic acid tolerance and lactic acid production in Saccharomyces cerevisiae

et al. 2014

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Background: The great interest in the production of highly pure lactic acid enantiomers comes from the application of polylactic acid (PLA) for the production of biodegradable plastics. Yeasts can be considered as alternative cell factories to lactic acid bacteria for lactic acid production, despite not being natural producers, since they can better tolerate acidic environments. We have previously described metabolically engineered Saccharomyces cerevisiae strains producing high amounts of L-lactic acid (>60 g/L) at low pH. The high product concentration represents the major limiting step of the process, mainly because of its toxic effects. Therefore, our goal was the identification of novel targets for strain improvement possibly involved in the yeast response to lactic acid stress.

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Section: Discussionsupporting

confidence: 72%

Changes in SAM 2 expression affect lactic acid tolerance and lactic acid production in Saccharomyces cerevisiae

et al. 2014

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“…There have also been multiple attempts to modify the specificity of NAD(P)H-dependent oxidoreductases for the cofactor they use for the electron transfer reaction, as controlling the cofactor specificity of this class of enzymes can be used to optimally engineer the cellular metabolism by achieving a better balance of cofactor availability [171,172]. During the last two decades, there have been a considerable number of successful cases of relaxation or even reversal of NADH/NADPH cofactor specificity.…”

Section: Protein Engineeringmentioning

confidence: 99%

Review of NAD(P)H-dependent oxidoreductases: Properties, engineering and application

Vidal

Kelly

Mordaka

et al. 2018

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

249

147

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A B S T R A C T NAD(P)H-dependent oxidoreductases catalyze the reduction or oxidation of a substrate coupled to the oxidation or reduction, respectively, of a nicotinamide adenine dinucleotide cofactor NAD(P)H or NAD(P) + . NAD(P)Hdependent oxidoreductases catalyze a large variety of reactions and play a pivotal role in many central metabolic pathways. Due to the high activity, regiospecificity and stereospecificity with which they catalyze redox reactions, they have been used as key components in a wide range of applications, including substrate utilization, the synthesis of chemicals, biodegradation and detoxification. There is great interest in tailoring NAD(P)H-dependent oxidoreductases to make them more suitable for particular applications. Here, we review the main properties and classes of NAD(P)H-dependent oxidoreductases, the types of reactions they catalyze, some of the main protein engineering techniques used to modify their properties and some interesting examples of their modification and application.

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“…Control of electron flow is essential to engineer metabolism for the production of desired outputs [39]. Key enzymes for maintaining redox balance are the hydrogenases, which can direct electron flow to proton reduction.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen-Cycling during Solventogenesis in Clostridium acetobutylicum American Type Culture Collection (ATCC) 824 Requires the [NiFe]-Hydrogenase for Energy Conservation

et al. 2018

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Clostridium acetobutylicum has traditionally been used for production of acetone, butanol, and ethanol (ABE). Butanol is a commodity chemical due in part to its suitability as a biofuel; however, the current yield of this product from biological systems is not economically feasible as an alternative fuel source. Understanding solvent phase physiology, solvent tolerance, and their genetic underpinning is key for future strain optimization of the bacterium. This study shows the importance of a [NiFe]-hydrogenase in solvent phase physiology. C. acetobutylicum genes ca_c0810 and ca_c0811, annotated as a HypF and HypD maturation factor, were found to be required for [NiFe]-hydrogenase activity. They were shown to be part of a polycistronic operon with other hyp genes. Hydrogenase activity assays of the ∆hypF/hypD mutant showed an almost complete inactivation of the [NiFe]-hydrogenase. Metabolic studies comparing ∆hypF/hypD and wild type (WT) strains in planktonic and sessile conditions indicated the hydrogenase was important for solvent phase metabolism. For the mutant, reabsorption of acetate and butyrate was inhibited during solventogenesis in planktonic cultures, and less ABE was produced. During sessile growth, the ∆hypF/hypD mutant had higher initial acetone: butanol ratios, which is consistent with the inability to obtain reduced cofactors via H 2 uptake. In sessile conditions, the ∆hypF/hypD mutant was inhibited in early solventogenesis, but it appeared to remodel its metabolism and produced mainly butanol in late solventogenesis without the uptake of acids. Energy filtered transmission electron microscopy (EFTEM) mapped Pd(II) reduction via [NiFe]-hydrogenase induced H 2 oxidation at the extracelluar side of the membrane on WT cells. A decrease of Pd(0) deposits on ∆hypF/hypD comparatively to WT indicates that the [NiFe]-hydrogenase contributed to the Pd(II) reduction. Calculations of reaction potentials during acidogenesis and solventogenesis predict the [NiFe]-hydrogenase can couple NAD + reduction with membrane transport of electrons. Extracellular oxidation of H 2 combined with the potential for electron transport across the membrane indicate that the [NiFe}-hydrogenase contributes to proton motive force maintenance via hydrogen cycling.

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Cofactor engineering for advancing chemical biotechnology

Cited by 138 publications

References 59 publications

Changes in SAM 2 expression affect lactic acid tolerance and lactic acid production in Saccharomyces cerevisiae

Changes in SAM 2 expression affect lactic acid tolerance and lactic acid production in Saccharomyces cerevisiae

Review of NAD(P)H-dependent oxidoreductases: Properties, engineering and application

Hydrogen-Cycling during Solventogenesis in Clostridium acetobutylicum American Type Culture Collection (ATCC) 824 Requires the [NiFe]-Hydrogenase for Energy Conservation

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