The Reduction of 5-Oxodecanoic Acid by Normal Baker's Yeast

Francke, Alexander

doi:10.1042/bj0950633

Cited by 25 publications

(5 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Baker's yeast ( Saccharomyces cerevisiae ) has been the most popular whole-cell biocatalyst, particularly for asymmetric reductions of carbonyl compounds. − Reductions catalyzed by this organism tolerate a large diversity of carbonyl substrates, and side reactions are rarely observed. This broad substrate acceptance is due to the presence of a number of reductase enzymes, several of which have been isolated and characterized. − Unfortunately, some of these reductases possess overlapping substrate specificities but with opposite enantioselectivities, which often diminishes the optical purities of the alcohol products when a compound is accepted by multiple enzymes. Traditional approaches to overcoming these problems have included variations in substrate structure and concentration, the use of organic solvents in place of water, − heat treatment, and the addition of exogenous modifiers. ,− With the recent determination of the complete genome sequence of S. cerevisiae , altering the enantioselectivities of whole-cell-mediated reductions by genetic manipulation has become a feasible goal.…”

Section: Introductionmentioning

confidence: 99%

Baker's Yeast-Mediated Reductions of α-Keto Esters and an α-Keto-β-Lactam. Two Routes to the Paclitaxel Side Chain

et al. 1999

View full text Add to dashboard Cite

Baker's yeast (Saccharomyces cerevisiae) has been used to reduce a series of alkyl esters derived from pyruvate and benzoylformate. Both the yield and enantioselectivities of these reductions were maximized when methyl esters were used, and the (R)-alcohols were isolated in all instances. Yeastmediated ester hydrolysis was a significant side reaction for products derived from long-chain alcohols. In the case of ethyl benzoylformate, the addition of methyl vinyl ketone increased the enantioselectivity of the reduction. These reductions were applied to two syntheses of the paclitaxel C 13 side chain [(2R,3S)-N-benzoyl-3-phenylisoserine]. In the first, a racemic R-keto-β-azido ester was reduced by whole cells of Baker's yeast to afford a diastereomeric mixture in which the desired product predominated and could be isolated chromatographically. In the second, an easily synthesized R-keto-β-lactam was reduced by yeast cells to afford the desired cis isomer as well as the undesired trans diastereomer. Substituting a yeast strain deficient in fatty acid synthase in this reduction suppressed formation of the trans diastereomer. These results suggest that a single enzyme is responsible for both the D-and L-cis-alcohols resulting from reduction of the R-keto-βlactam. All of the yeast strains used in this project are available commercially, and these biocatalytic reductions require only common laboratory equipment.

show abstract

Section: Introductionmentioning

confidence: 99%

Baker's Yeast-Mediated Reductions of α-Keto Esters and an α-Keto-β-Lactam. Two Routes to the Paclitaxel Side Chain

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Chiral hydroxy acids, their esters and lactones are building blocks of great value and interest for the synthesis of antibiotics, inhibitors, pharmaceuticals and pheromones of high enantiomeric purity (Chiba et al 1985;Georg and Kant 1988;Ehrler et al 1986;Francke 1965;Furuichi et al 1985;Gessner et al 1987;Hirama and Uei 1982;Hummel and Kula 1989a;Itoh et al 1987;Mori 1989;Mori and Sugai 1983;Oguni and Ohkawa 1988;Seebach and Zfiger 1982;Seebach et al 1984;Shimizu et al 1990;Utaka et al 1987). Today, hydroxy acids and esters are prepared on a laboratory scale predominantly by microbial reduction of the corresponding keto compound with excess baker's yeast (Christen and Crout 1987;Ward and Young 1990).…”

Section: Introductio'llmentioning

confidence: 99%

Studies on the distribution and regulation of microbial keto ester reductases

Peters

Zelinski

Kula

1992

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

In a limited screening 65 microorganisms were tested with regard to their ability to reduce keto acids or esters of different chain length and position of the keto group with NADH or NADPH as coenzymes. Twentyseven organisms exhibited reductase activity. Among these, Candida parapsilosis and Rhodococcus erythropolis have been chosen for further investigation. The keto ester reductases of both C. parapsilosis and R. erythropolis prefer NADH as coenzyme and show higher activity towards keto esters than keto acids. The keto ester reductase production of C. parapsilosis during growth passed a maximum in the late exponential phase, decreased and reaches a plateau in the stationary phase. In contrast, the specific activity of the keto ester reductase of R. erythropolis did not decrease in the stationary growth phase. The enzyme of C. parapsilosis was inducible by a keto ester when growing on glycerol as the sole carbon source. Furthermore, the enzyme of C. parapsilosis was subject to catabolite repression. When C. parapsilosis and R. erythropolis were cultivated on nalcane the specific activity of their keto ester reductases was enhanced about seven-and eightfold, respectively, compared to growth on glucose. This leads to the assumption that, while growing on n-alcane, a degradation product is formed in both strains that induces the production of the keto ester reductase.

show abstract

“…This enzyme activity was previously described by Franke [41] as NADPH-dependent and mitochondrial, but we failed to identify this enzyme in yeast cell extracts.…”

Section: Discussion (R) -Diucetyl Reductasementioning

confidence: 55%

Purification and properties of two oxidoreductases catalyzing the enantioselective reduction of diacetyl and other diketones from baker's yeast

Heidlas

Tressl

1990

European Journal of Biochemistry

View full text Add to dashboard Cite

The NADPH-linked diacetyl reductase system from the cytosolic fraction of Saccharomyces cerevisiae has been resolved into two oxidoreductases catalyzing irreversibly the enantioselective reduction of diacetyl (2,3-butanedione) to (9-and (R)-acetoin (3-hydroxy-2-butanone) [so-called (S)-and (R)-diacetyl reductases] (EC 1.1.1.5) which have been isolated to apparent electrophoretical purity.The clean-up procedures comprising streptomycin sulfate treatment, Sephadex G-25 filtration, DEAESepharose CL-6B column chromatography, affinity chromatography on Matrex Gel Red A and Superose 6 prep grade filtration led to 120-fold and 368-fold purifications, respectively.The relative molecular mass of the (R)-diacetyl reductase, estimated by means of HPLC filtration on Zorbax G F 250 and sodium dodecyl sulfate/polyacrylamide gel electrophoresis, was 36 000. The (R)-enzyme was most active at pH 6.4 and accepted in addition to diacetyl C5-, C6-2,3-diketones, 1,2-~yclohexanedione, 2-0x0 aldehydes and short-chain 2-and 3-0x0 esters as substrates. The enzyme was characterized by high enantioselectivity and regiospecificity. The K,,, values for diacetyl and 2,3-pentanedione were determined as 2.0 mM.The M , of the (3-diacetyl reductase was determined as 75000 by means of HPLC filtration on Zorbax G F 250. The enzyme decomposed into subunits of M , 48000 and 24000 on sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The optimum pH was 6.9. The purified @)-enzyme reduced stereospecifically a broad spectrum of substrates, comprising 2,3-, 2,4-and 2,5-diketones, %-ox0 aldehydes, 1 ,2-cyclohexanedione and methyl ketones as well as 3-, 4-and 5-0x0 esters. The 2,3-and 2,4-diketones are transformed to the corresponding (S)-2-hydroxy ketones; 2,5-hexanedione, however, was reduced to (S,S)-2,5-hexanediol. The K,,, values for diacetyl and 2,3-pentanedione were estimated as 2.3 and 1.5 mM, respectively. Further characterization of the (S)-diacetyl reductase revealed that it is identical with the so-called'(S)-enzyme', involved in the enantioselective reduction of 3-, 4-and 5-0x0 esters in baker's yeast.From the pioneering work of Neuburg and Nord [l], it is known that preparative reductions of diacetyl by actively fermenting baker's yeast lead to levorotary 2,3-butanediol. Various phytochemical transformations of diacetyl homologues and diketo compounds have been applied to obtain optically active hydroxy ketones and diols, useful building blocks in organic chemistry [2,3]. Diacetyl is also a physiological metabolite mainly formed in yeast by the chemical oxidative decarboxylation of 2-acetolactate, an intermediate in the biosynthesis of valine and leucine [4-71. It is responsible for the well-known off-flavor called 'buttery note' in fermented beverages, especially beer 181.The importance of diacetyl in the brewing process has been a major reason for various investigations of the enzymes involved in its reduction to acetoin (so-called diacetyl reductases) and further to 2,3-butanediol (2,3-butanediol deCorrespondence to J. Heidlas,

show abstract

The Reduction of 5-Oxodecanoic Acid by Normal Baker's Yeast

Cited by 25 publications

References 16 publications

Baker's Yeast-Mediated Reductions of α-Keto Esters and an α-Keto-β-Lactam. Two Routes to the Paclitaxel Side Chain

Baker's Yeast-Mediated Reductions of α-Keto Esters and an α-Keto-β-Lactam. Two Routes to the Paclitaxel Side Chain

Studies on the distribution and regulation of microbial keto ester reductases

Purification and properties of two oxidoreductases catalyzing the enantioselective reduction of diacetyl and other diketones from baker's yeast

Contact Info

Product

Resources

About