- Better than Nature: Nicotinamide Biomimetics That Outperform Natural Coenzymes
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The search for affordable, green biocatalytic processes is a challenge for chemicals manufacture. Redox biotransformations are potentially attractive, but they rely on unstable and expensive nicotinamide coenzymes that have prevented their widespread expl
- Knaus, Tanja,Paul, Caroline E.,Levy, Colin W.,De Vries, Simon,Mutti, Francesco G.,Hollmann, Frank,Scrutton, Nigel S.
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- On the bi-enzymatic behaviour of Saccharomyces cerevisiae-mediated stereoselective biotransformation of 2,6,6-trimethylcyclohex-2-ene-1,4-dione
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Baker's yeast has been well-known to have the ability to reduce a variety of substrates into many optically active compounds. One of the important chemicals is (4R,6R)-4-hydroxy-2,2,6-trimethylcyclohexanone or in short, (4R,6R)-actinol, a product formed f
- Uzir, Mohamad Hekarl,Najimudin, Nazalan
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Read Online
- Metals in Biotechnology: Cr-Driven Stereoselective Reduction of Conjugated C=C Double Bonds
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Elemental metals are shown to be suitable sacrificial electron donors to drive the stereoselective reduction of conjugated C=C double bonds using Old Yellow Enzymes as catalysts. Both direct electron transfer from the metal to the enzyme as well as mediated electron transfer is feasible, although the latter excels by higher reaction rates. The general applicability of this new chemoenzymatic reduction method is demonstrated, and current limitations are outlined.
- Rauch, Marine C. R.,Gallou, Yann,Delorme, Léna,Paul, Caroline E.,Arends, Isabel W. C. E.,Hollmann, Frank
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p. 1112 - 1115
(2019/12/27)
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- Engineering a nicotinamide mononucleotide redox cofactor system for biocatalysis
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Biological production of chemicals often requires the use of cellular cofactors, such as nicotinamide adenine dinucleotide phosphate (NADP+). These cofactors are expensive to use in vitro and difficult to control in vivo. We demonstrate the development of a noncanonical redox cofactor system based on nicotinamide mononucleotide (NMN+). The key enzyme in the system is a computationally designed glucose dehydrogenase with a 107-fold cofactor specificity switch toward NMN+ over NADP+ based on apparent enzymatic activity. We demonstrate that this system can be used to support diverse redox chemistries in vitro with high total turnover number (~39,000), to channel reducing power in Escherichia coli whole cells specifically from glucose to a pharmaceutical intermediate, levodione, and to sustain the high metabolic flux required for the central carbon metabolism to support growth. Overall, this work demonstrates efficient use of a noncanonical cofactor in biocatalysis and metabolic pathway design.
- Black, William B.,Zhang, Linyue,Mak, Wai Shun,Maxel, Sarah,Cui, Youtian,King, Edward,Fong, Bonnie,Sanchez Martinez, Alicia,Siegel, Justin B.,Li, Han
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- Synthesis and Biochemical Evaluation of Nicotinamide Derivatives as NADH Analogue Coenzymes in Ene Reductase
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Nicotinamide and pyridine-containing conjugates have attracted a lot of attention in research as they have found use in a wide range of applications including as redox flow batteries and calcium channel blockers, in biocatalysis, and in metabolism. The interesting redox character of the compounds’ pyridine/dihydropyridine system allows them to possess very similar characteristics to the natural chiral redox agents NAD+/NADH, even mimicking their functions. There has been considerable interest in designing and synthesizing NAD+/NADH mimetics with similar redox properties. In this research, three nicotinamide conjugates were designed, synthesized, and characterized. Molecular structures obtained through X-ray crystallography were obtained for two of the conjugates, thereby providing more detail on the bonding and structure of the compounds. The compounds were then further evaluated for biochemical properties, and it was found that one of the conjugates possessed similar functions and characteristics to the natural NADH. This compound was evaluated in the active enzyme, enoate reductase; like NADH, it was shown to help reduce the C=C double bond of three substrates and even outperformed the natural coenzyme. Kinetic data are reported.
- Falcone, Natashya,She, Zhe,Syed, Jebreil,Lough, Alan,Kraatz, Heinz-Bernhard
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p. 838 - 845
(2019/02/07)
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- Highly efficient aqueous phase chemoselective hydrogenation of α,β-unsaturated aldehydes catalysed by phosphine-decorated polymer immobilized IL-stabilized PdNPs
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Phosphino-decorated polymer immobilised ionic liquid phase stabilised palladium nanoparticles (PdNP@PPh2-PIILP) and their PEGylated counterparts (PdNP@PPh2-PEGPIILP) are remarkably active and exceptionally selective catalysts for the aqueous phase hydrogenation of α,β-unsaturated aldehydes, ketones, esters and nitriles with PdNP@PPh2-PEGPIILP giving complete conversion and 100% selectivity for reduction of the CC bond, under mild conditions. This is the most selective PdNP-based system to be reported for the aqueous phase hydrogenation of this class of substrates.
- Doherty,Knight,Backhouse,Abood,Alshaikh,Fairlamb,Bourne,Chamberlain,Stones
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supporting information
p. 1635 - 1641
(2017/06/05)
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- Structural insights into the ene-reductase synthesis of profens
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Reduction of double bonds of α,β-unsaturated carboxylic acids and esters by ene-reductases remains challenging and it typically requires activation by a second electron-withdrawing moiety, such as a halide or second carboxylate group. We showed that profen precursors, 2-arylpropenoic acids and their esters, were efficiently reduced by Old Yellow Enzymes (OYEs). The XenA and GYE enzymes showed activity towards acids, while a wider range of enzymes were active towards the equivalent methyl esters. Comparative co-crystal structural analysis of profen-bound OYEs highlighted key interactions important in determining substrate binding in a catalytically active conformation. The general utility of ene reductases for the synthesis of (R)-profens was established and this work will now drive future mutagenesis studies to screen for the production of pharmaceutically-active (S)-profens.
- Waller,Toogood,Karuppiah,Rattray,Mansell,Leys,Gardiner,Fryszkowska,Ahmed,Bandichhor,Reddy,Scrutton
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p. 4440 - 4448
(2017/07/10)
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- Light-driven biocatalytic reduction of α,β-unsaturated compounds by ene reductases employing transition metal complexes as photosensitizers
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Efficient and cost effective nicotinamide cofactor regeneration is essential for industrial-scale bio-hydrogenations employing flavin-containing biocatalysts such as the Old Yellow Enzymes. A direct flavin regeneration system using visible light to initiate a photoredox cycle and drive biocatalysis is described, and shown to be effective in driving biocatalytic activated alkene reduction. Using Ru(ii) or Ir(iii) complexes as photosensitizers, coupled with an electron transfer mediator (methyl viologen) and sacrificial electron donor (triethanolamine) drives catalytic turnover of two Old Yellow Enzymes with multiple oxidative substrates. Therefore, there is great potential in the development of light-driven biocatalytic systems, providing an alternative to the reliance on enzyme-based cofactor regeneration systems.
- Peers, Martyn K.,Toogood, Helen S.,Heyes, Derren J.,Mansell, David,Coe, Benjamin J.,Scrutton, Nigel S.
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p. 169 - 177
(2015/12/31)
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- Two "classical" Old Yellow Enzymes from Chryseobacterium sp. CA49: Broad substrate specificity of Chr-OYE1 and limited activity of Chr-OYE2
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Two putative Old Yellow Enzyme (OYE) homologues, Chr-OYE1 and Chr-OYE2, were identified from the genome of Chryseobacterium sp. CA49 as new members of the "classical" subfamily. Chr-OYE1 and Chr-OYE2 were most closely related to the SYE4 from Shewanella oneidensis and NerA from Agrobacterium radiobacter with 41% and 45% identity, respectively. Both enzymes were expressed in Escherichia coli in soluble form, but their catalytic abilities as ene-reductases were quite different. Among the 19 substrate tested, Chr-OYE1 could catalyze the reduction of 18 of them including an ynone with excellent stereoselectivity for several prochiral ones, and its specific activity was roughly 1100-fold high than Chr-OYE2, which only catalyzed 3 of the substrates. After restoring the conserved tyrosine, Chr-OYE2 remained the same substrate spectrum, but showed significantly enhanced activity and stereoselectivity.
- Pei, Xiao-Qiong,Xu, Meng-Yu,Wu, Zhong-Liu
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- The substrate spectra of pentaerythritol tetranitrate reductase, morphinone reductase, N-ethylmaleimide reductase and estrogen-binding protein in the asymmetric bioreduction of activated alkenes
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Four flavoproteins from the old yellow enzyme (OYE) family, pentaerythritol tetranitrate (PETNR) reductase, N-ethylmaleimide reductase (NEMR), morphinone reductase (MorR) and estrogen-binding protein (EBP1), exhibited a broad substrate tolerance by accepting conjugated enals, enones, imides, dicarboxylic acids and esters, as well as a nitroalkene and therefore can be employed for the asymmetric bioreduction of carbon-carbon double (C=C) bonds. In particular, morphinone reductase and estrogen-binding protein often showed a complementary stereochemical preference in comparison to that of previously investigated OYES.
- Mueller, Nicole J.,Stueckler, Clemens,Hauer, Bernhard,Baudendistel, Nina,Housden, Hazel,Bruce, Neil C.,Faber, Kurt
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experimental part
p. 387 - 394
(2010/06/11)
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- Conjugate reduction of α,β-unsaturated ketones using an Mn(III) catalyst, phenylsilane and isopropyl alcohol
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Treatment of a variety of α,β-unsaturated ketones with Mn(dpm)3 (3 mol%)/PhSiH3 (1.3 equiv.)/isopropyl alcohol with the exclusion of air resulted in the formation of the saturated ketone. (C) 2000 Elsevier Science Ltd.
- Magnus,Waring,Scott
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p. 9731 - 9733
(2007/10/03)
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- Structure-odor correlation, XXIV: Synthesis and olfactory properties of damascene and damascenone analogs
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The aldehydes rac-1, rac-2, and 3 were conveniently prepared by starting from isophorone (4). Reaction of 1-3 with (E,Z)-1-bromo-1-propene (14) afforded the rac-allylic alcohols (E,Z)-15, -18, and -20. The alcohols were oxidized to the damascone/damascenone analogs 1-(3,5,5-trimethyl-2-cyclohexen-1-yl)- (rac-16), 1-(3,5,5-trimethyl-1-cyclohexen-1-yl)-(rac-19), and 1-(3,5,5-trimethyl-1,3-cyclohexadien-1-yl)-2-buten-1-one (21), and the (E/Z) isomers were separated by FC. Their olfactory evaluation shows that the highly estimated odor of damascone (A, B) and damascenone (C) is more or less lost. This result can be explained by force-field calculation of the lowest energy conformation of 16, 19, and 21 in comparison with those of A-C. VCH Verlagsgesellschaft mbH, 1996.
- Weyerstahl, Peter,Licha, Kai
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p. 809 - 814
(2007/10/03)
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- 3-OXO-α-IONOL, VOMIFOLIOL AND ROSEOSIDE IN VITIS VINIFERA FRUIT
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Key Word Index - Vitis vinifera; Vitaceae; grapes; 3-oxo-α-ionol; vomifoliol; dehydrovomifoliol; roseoside; hydrolytic studies. 3-Oxo-α-ionol, vomifoliol and dehydrovomifoliol were identified for the first time in fruit from Vitis vinifera.The last named compound was mainly present free in the juice while the others existed predominantly as conjugates.In the case of vomifoliol, the conjugation was with glucose, i.e. as roseoside.Hydrolytic studies on 3-oxo-α-ionol and vomifoliol gave a range of compounds which have been recognized as fruit and plant products.
- Strauss, Christopher R.,Wilson, Bevan,Williams, Patrick J.
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p. 1995 - 1998
(2007/10/02)
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