Stereochemical control of yeast reductions. 5. Characterization of the oxidoreductases involved in the reduction of .beta.-keto esters

Shieh, Woan‐Ru; Gopalan, Aravamudan S.; Sih, Charles J.

doi:10.1021/ja00296a038

Cited by 214 publications

(52 citation statements)

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“…In general NADH-dependent carbonyl reductases also have alcohol dehydrogenase activity. 36,37) Alternatively, almost all NADPH-dependent carbonyl reductases 6,8,[13][14][15][16][17][18] only have reductase activities but no dehydrogenase activities. In principle, carbonyl reductases that cannot catalyze oxidative reactions are more advantageous to asymmetric reduction than alcohol dehydrogenases that can catalyze oxido-reductive reactions because the equilibration of a reaction is not necessary for consideration.…”

Section: Discussionmentioning

confidence: 99%

“…Tel: +81-29-856-1322; Fax: +81-29-856-1323; E-mail: h-yamamoto@daicel.co.jp Abbreviations: ADH, alcohol dehydrogenase; CR, carbonyl reductase; KaCR1, carbonyl reductase 1 from Kluyveromyces aestuarii; ECAA, ethyl 4-chloroacetoacetate; ECHB, ethyl 3-hydroxybutanoate; FDH, formate dehydrogenase; GDH, glucose dehydrogenase inhibitors 11) and 4-hydroxypyrrolidone. 12) Several enzymes reducing ethyl 4-chloroacetoacetate (ECAA) to (S)-ECHB have been found and purified from Candida macedoniensis, 13) Candida magnoliae, 14) Geotrichum candidum, 15) Kluyveromyces lactis, 16) Saccharomyces cerevisiae, 17) and S. salmonicolor; 18) furthermore, -ketoacyl-acyl carrier protein (ACP) reductases and acetoacetyl-CoA reductases were reported to reduce ECAA to (S)-ECHB with high enantioselectivity. 8) All of the carbonyl reductases listed above, however, were NADPH-dependent and the regeneration of a coenzyme using FDH cannot be applied to the production of (S)-ECHB using these enzymes.…”

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A Novel NADH-Dependent Carbonyl Reductase fromKluyveromyces aestuariiand Comparison of NADH-Regeneration System for the Synthesis of Ethyl (S)-4-Chloro-3-hydroxybutanoate

Yamamoto¹,

Mitsuhashi²,

Kimoto³

et al. 2004

Bioscience, Biotechnology, and Biochemistry

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

A Novel NADH-Dependent Carbonyl Reductase fromKluyveromyces aestuariiand Comparison of NADH-Regeneration System for the Synthesis of Ethyl (S)-4-Chloro-3-hydroxybutanoate

Yamamoto¹,

Mitsuhashi²,

Kimoto³

et al. 2004

Bioscience, Biotechnology, and Biochemistry

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“…18 Baker's yeast expresses several reducing enzymes which can be selectively inhibited or favoured by varying the reaction conditions. 19 Pretreatment of the yeast with cross-linking agents such as methyl-vinyl ketone (MVK), was found to favor syn-selectivity and prevent over-reduction to the diol. 20 Heat-denaturation (50°C, 30 min) also achieved the same goal and even worked synergistically with MVK.…”

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confidence: 99%

Stereochemical modification of geminal dialkyl substituents on pantothenamides alters antimicrobial activity

Hoegl¹,

Darabi²,

Tran³

et al. 2014

Bioorganic & Medicinal Chemistry Letters

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Pantothenamides are N-substituted pantothenate derivatives which are known to exert antimicrobial activity through interference with coenzyme A (CoA) biosynthesis or downstream CoA-utilizing proteins. A previous report has shown that replacement of the ProR methyl group of the benchmark N-pentylpantothenamide with an allyl group (R-anti configuration) yielded one of the most potent antibacterial pantothenamides reported so far (MIC of 3.2 μM for both sensitive and resistant Staphylococcus aureus). We describe herein a synthetic route for accessing the corresponding R-syn diastereomer using a key diastereoselective reduction with Baker's yeast, and report on the scope of this reaction for modified systems. Interestingly, whilst the R-anti diastereomer is the only one to show antibacterial activity, the R-syn isomer proved to be significantly more potent against the malaria parasite (IC 50 of 2.4 ± 0.2 μM). Our research underlines the striking influence that stereochemistry has on the biological activity of pantothenamides, and may find utility in the study of various CoA-utilizing systems. Keywordspantothenamides; antibacterial; antiplasmodial; baker's yeast; coenzyme A Infectious diseases remain a major contributing factor to worldwide mortality. Moreover, the development of antimicrobial resistance is raising significant concerns about the increasingly limited efficacy of currently available treatments. 1 There have been considerable efforts towards discovering and characterising novel therapeutic targets for antimicrobial drugs. One such target which has emerged as a promising point-of-attack is

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“…[7][8][9] Furthermore, several yeast keto ester reductases (YKERs) were isolated from bakers' yeast and their enzymatic properties studied including the speciˆc activity, stereoselectivity, and kinetic parameters. [10][11][12][13][14] Other microorganisms such as Thermoanaerobactor brockii, 15) Geotrichum candidum, 16,17) and Klebsiella pneumoniae 18) that can also catalyze the asymmetric reduction of keto esters are also used for the preparation of chiral hydroxy esters. However, little information is known from mechanistic studies of enzymatic reduction by their microorganisms.…”

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confidence: 99%

Purification and Characterization of Two α-Keto Ester Reductases fromStreptomyces thermocyaneoviolaceusIFO 14271

Yamaguchi

Nakajima²,

Ishihara

2002

Bioscience, Biotechnology, and Biochemistry

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Two NADPH-dependent a-keto ester reductases (Streptomyces thermocyaneoviolaceus keto ester reductase, STKER-II and -III) were puriˆed from S. thermocyaneoviolaceus IFO 14271, one of thermophilic actinomycetes. The molecular masses of native STKER-II and -III were estimated to be 60 kDa and 70 kDa by gel ltration chromatography, respectively. These enzymes were both homodimers, with 29-kDa and 30-kDa subunit molecular masses based on SDS polyacrylamide gel electrophoresis. STKER-II and -III were stable from pH 7.0 to 10.0 and pH 5.5 to 9.0, respectively. Ethyl 3-methyl-2-oxobutanoate was reduced by both enzymes isolated to the corresponding (R)-hydroxy ester with excellent enantiomeric excess. STKER-III showed high stereoselectivity for the reduction of bulky substrates, while the selectivity of the STKER-II-catalyzed reduction was low except for ethyl 3-methyl-2-hydroxybutanoate. Both enzymes had small K m values toward aliphatic keto esters having a long alkyl chain.

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Stereochemical control of yeast reductions. 5. Characterization of the oxidoreductases involved in the reduction of .beta.-keto esters

Cited by 214 publications

References 2 publications

A Novel NADH-Dependent Carbonyl Reductase fromKluyveromyces aestuariiand Comparison of NADH-Regeneration System for the Synthesis of Ethyl (S)-4-Chloro-3-hydroxybutanoate

A Novel NADH-Dependent Carbonyl Reductase fromKluyveromyces aestuariiand Comparison of NADH-Regeneration System for the Synthesis of Ethyl (S)-4-Chloro-3-hydroxybutanoate

Stereochemical modification of geminal dialkyl substituents on pantothenamides alters antimicrobial activity

Purification and Characterization of Two α-Keto Ester Reductases fromStreptomyces thermocyaneoviolaceusIFO 14271

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