Whole-cell yeast-mediated preparation of (R)-2-chloro-1-(3-nitrophenyl)ethanol as a synthetic precursor for (R)-phenylephrine

Tokoshima, Daisuke; Hanaya, Kengo; Shoji, Mitsuru; Sugai, Takeshi

doi:10.1016/j.molcatb.2013.07.021

Cited by 14 publications

(8 citation statements)

References 18 publications

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“…Despite the fact that the strains of Y. lipolytica contain less selective alcohol dehydrogenases than some other biocatalysts catalyzing the enantioselective reduction of acetophenone and its halogen derivatives (Lin et al 2009 ; Tokoshima et al 2013 ), they do have a rare ability to reduce acetophenone to the anti-Prelog R -alcohol. However, the aim of our study, apart from presenting the capability of selected strains to perform the effective reduction, was to show differences in biocatalytic properties of strains within the same species.…”

Section: Resultsmentioning

confidence: 99%

Biotransformation of acetophenone and its halogen derivatives by Yarrowia lipolytica strains

et al. 2014

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The ability of 16 strains of Yarrowia lipolytica to biotransform acetophenone and its derivatives has been studied. Thirteen of these strains were derived from a wild-type strain Y. lipolytica A-101; six had the invertase gene (SUC2) from Saccharomyces cerevisiae integrated into their genome, as well as the damaged or undamaged gene encoding orotidine-5′-phosphate decarboxylase (URA3), three had integrated the damaged URA3 gene into their genome and three were UV acetate-negative mutants, not able to growth on acetate as the sole carbon source. The other tested strains included two wild strains, A-101 and PMR-1, and an adenine auxotroph ATCC 32-338A. All strains were capable of reducing acetophenone to the R-alcohol in high enantiomeric excess (80–89 %). In all of the cultures tested, reversibility of the reduction was observed, which led to an increase in the enantiomeric excess. nantioselective reduction of the acetophenone halogen derivatives revealed that the nature and location of the halogen atom had a significant influence on the enantioselectivity of the reduction. In the culture of ATCC 32-338A, after a 3-day biotransformation of 2,4′-dibromoacetophenone the enantiopure R-alcohol was obtained at a rate of 100 % of substrate conversion. In conclusion, using these invertase-containing strains or uracyl auxotrophs provided no additional benefit in terms of biotransformation capacity over the parental strain.

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Section: Resultsmentioning

confidence: 99%

Biotransformation of acetophenone and its halogen derivatives by Yarrowia lipolytica strains

et al. 2014

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“…Furthermore, the manufacture of valuable enantiomers for different industries [25] could represent an application for this biocatalyst, both in in vivo and in vitro systems. The compatibility of chemically resistant Fdhs in productive processes has already been shown with the precursors of statins [12], encouraging the use of such enzymes for pathways whose synthetic steps have the same chemistry, such as adrenergic receptor agonists or selective serotonin reuptake inhibitors [64][65][66]. Likewise, Fdh SNO could prove to be a suitable tool for enzymatic or microbial bioremediation of sites contaminated by chemical and metal pollutants [67][68][69], avoiding the exhaustion of the reduced cofactor pool that supports the biodegradation process.…”

Section: Discussionmentioning

confidence: 99%

Biochemical and structural insight into the chemical resistance and cofactor specificity of the formate dehydrogenase from Starkeya novella

et al. 2023

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Formate dehydrogenases (Fdhs) mediate the oxidation of formate to carbon dioxide and concomitant reduction of nicotinamide adenine dinucleotide (NAD+). The low cost of the substrate formate and importance of the product NADH as a cellular source of reducing power make this reaction attractive for biotechnological applications. However, the majority of Fdhs are sensitive to inactivation by thiol‐modifying reagents. In this study, we report a chemically resistant Fdh (FdhSNO) from the soil bacterium Starkeya novella strictly specific for NAD+. We present its recombinant overproduction, purification and biochemical characterization. The mechanistic basis of chemical resistance was found to be a valine in position 255 (rather than a cysteine as in other Fdhs) preventing the inactivation by thiol‐modifying compounds. To further improve the usefulness of FdhSNO as for generating reducing power, we rationally engineered the protein to reduce the coenzyme nicotinamide adenine dinucleotide phosphate (NADP+) with better catalytic efficiency than NAD+. The single mutation D221Q enabled the reduction of NADP+ with a catalytic efficiency kCAT/KM of 0.4 s−1·mm−1 at 200 mm formate, while a quadruple mutant (A198G/D221Q/H379K/S380V) resulted in a fivefold increase in catalytic efficiency for NADP+ compared with the single mutant. We determined the cofactor‐bound structure of the quadruple mutant to gain mechanistic evidence behind the improved specificity for NADP+. Our efforts to unravel the key residues for the chemical resistance and cofactor specificity of FdhSNO may lead to wider use of this enzymatic group in a more sustainable (bio)manufacture of value‐added chemicals, as for instance the biosynthesis of chiral compounds.

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“…For example, they can be convertible to congestive heart failure drug ( R )‐denopamine,, clinically potent β‐adrenoreceptor agonist and sympathomimetic drug ( R )‐isoproterenol and α 1 ‐adrenergic receptor agonist ( R )‐phenylephrine . In addition, growing protocols have been developed for the transformations of enantioenriched halohydrins into a broad range of functional groups to construct various useful chiral organic compounds, such as epoxides,–, hydroxynitriles,– azides,– glycols and amino alcohols ,–. Therefore, the methods introducing chiral halohydrin motifs with excellent stereocontrol provided a powerful platform for asymmetric synthesis.…”

Section: Methodsmentioning

confidence: 99%

Iridium‐Catalyzed Asymmetric Hydrogenation of Halogenated Ketones for the Efficient Construction of Chiral Halohydrins

Yin

et al. 2018

Adv Synth Catal

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Iridium-catalyzed asymmetric hydrogenation of prochiral halogenated ketones was successfully developed to prepare various chiral halohydrins with high reactivities and excellent enantioselectivities under basic reaction condition (up to > 99% conversion, 99% yield, > 99% ee). Moreover, gram-scale experiment was performed well in the presence of just 0.005 mol% (S/C = 20 000) Ir/f-amphox catalyst with 99% yield and > 99% ee.

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Whole-cell yeast-mediated preparation of (R)-2-chloro-1-(3-nitrophenyl)ethanol as a synthetic precursor for (R)-phenylephrine

Cited by 14 publications

References 18 publications

Biotransformation of acetophenone and its halogen derivatives by Yarrowia lipolytica strains

Biotransformation of acetophenone and its halogen derivatives by Yarrowia lipolytica strains

Biochemical and structural insight into the chemical resistance and cofactor specificity of the formate dehydrogenase from Starkeya novella

Iridium‐Catalyzed Asymmetric Hydrogenation of Halogenated Ketones for the Efficient Construction of Chiral Halohydrins

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