Abstract
Biotransformation of benzaldehyde to l-phenylacetylcarbinol (l-PAC) as a key intermediate for l-ephedrine synthesis has been evaluated using immobilized Candida utilis. During biotransformation, the benzaldehyde level and respiratory quotient significantly affected both l-PAC and by-product benzyl alcohol formation. By controlling the benzaldehyde level at 2 g/l, maintaining a respiratory quotient of 5–7 and pulse feeding glucose, a final concentration of 15.2 g/l l-PAC was achieved in a fed-batch process. This compares with previous published results of 10–12 g/l in batch culture and 10 g/l l-PAC in a semicontinuous process with immobilized Saccharomyces cerevisiae. In a single stage continuous process with immobilized C. utilis, the steady state l-PAC concentration was significantly reduced because of the sustained toxic effects of benzaldehyde.
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Astrup A, Breum L, Toubro S, Hein P, Quaade F (1992a) The effect and safety of an ephedrine-caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet: a double blind trial. Int J Obesity 16:269–277
Astrup A, Buemann B, Christensen NJ, Toubro S, Thoebek G, Victor OJ, Quaade F (1992b) The effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women. Metabolism 41:686–688
Bergmeyer HU (1974) Methods of enzymatic analysis, vol. 1. Academic Press New York and London, pp. 429–509
Bradford MM (1970) A rapid and sensitive method for the quantification of microgram quantities of protein, utilization of the principle of protein dye binding. Anal Biochem 72:248–254
Bringer-Meyer S, Sahm H (1988) Acetoin and phenylacetylcarbinol formation by the pyruvate decarboxylase of Zymomonas mobilis and Saccharomyces carlsbergensis. Biocatalysis 1:321–331
Culic K, Netrval J, Souhadra J, Ulbrecht S, Vojtisek V, Vodnansky MM (1984) Method of cost reduction in the production of d-(−)-1-phenyl-1-hydroxy-2-propane for the production of l-(−)ephedrine. Czechoslovakian patent 22,941
Long A, Ward OP (1989) Biotransformation of benzaldehyde by Saccharomyces cerevisiae: characterization of the fermentation and toxicity effects of substrates and products. Biotechnol Bioeng 34:933–941
Mahmoud WM, El-Sayed AdH MM, Coughlin RW (1990a) Production of l-phenylacetylcarbinol by immobilized yeast cells. I. Batch fermentation. Biotechnol Bioeng 36:47–54
Mahmoud WM, El-Sayed AdH MM, Coughlin RW (1990b) Production of l-phenylacetylcarbinol by immobilized yeast cells. II. Semicontinuous fermentation. Biotechnol Bioeng 36:55–63
Nikolova P, Ward OP (1991) Production of l-phenylacetylcarbinol by biotransformation: product and by-product formation and activities of the key enzymes in wild-type and ADH iso-enzyme mutants of Saccharomyces cerevisiae. Biotechnol Bioeng 38:493–498.
Seely RJ, Hefner DL, Hageman RW, Yarus MJ, Sullivan SA (1989) Process for making phenylacetylcarbinol (PAC), microorganisms for use in the process and a method for preparing the microorganisms. US Patent, PCT/US 89/04423
Vojtisek V, Netrval J (1982) Effect of PDC activity and pyruvate concentration on production of 1-hydroxy-1-phenylpropanol in Saccharomyces carlsbergensis. Folia Microbiol 27:173–177
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Shin, H.S., Rogers, P.L. Biotransformation of benzeldehyde to l-phenylacetylcarbinol, an intermediate in l-ephedrine production, by immobilized Candida utilis . Appl Microbiol Biotechnol 44, 7–14 (1995). https://doi.org/10.1007/BF00164473
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DOI: https://doi.org/10.1007/BF00164473