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An improved stereoselective reduction of a bicyclic diketone by Saccharomyces cerevisiae combining process optimization and strain engineering

Katz, Michael LU ; Sarvary, Ian LU ; Frejd, Torbjörn LU ; Hahn-Hägerdal, Bärbel LU and Gorwa-Grauslund, Marie-Francoise LU (2002) In Applied Microbiology and Biotechnology 59(6). p.641-648
Abstract
The stereoselective reduction of the bicyclic diketone bicyclo[2.2.2]octane-2,6-dione, to the ketoalcohol (1R,4S,6S)-6-hydroxybicyclo[2.2.2]octane-2-one, was used as a model reduction to optimize parameters involved in NADPH-dependent reductions in Saccharomyces cerevisiae with glucose as co-substrate. The co-substrate yield (ketoalcohol formed/glucose consumed) was affected by the initial concentration of bicyclic diketone, the ratio of yeast to glucose, the medium composition, and the pH. The reduction of 5 g l(-1) bicyclic diketone was completed in less than 20 h in complex medium (pH 5.5) under oxygen limitation with an initial concentration of 200 g l(-1) glucose and 5 g l(-1) yeast. The co-substrate yield was further enhanced by... (More)
The stereoselective reduction of the bicyclic diketone bicyclo[2.2.2]octane-2,6-dione, to the ketoalcohol (1R,4S,6S)-6-hydroxybicyclo[2.2.2]octane-2-one, was used as a model reduction to optimize parameters involved in NADPH-dependent reductions in Saccharomyces cerevisiae with glucose as co-substrate. The co-substrate yield (ketoalcohol formed/glucose consumed) was affected by the initial concentration of bicyclic diketone, the ratio of yeast to glucose, the medium composition, and the pH. The reduction of 5 g l(-1) bicyclic diketone was completed in less than 20 h in complex medium (pH 5.5) under oxygen limitation with an initial concentration of 200 g l(-1) glucose and 5 g l(-1) yeast. The co-substrate yield was further enhanced by genetically engineered strains with reduced phosphoglucose isomerase activity and with the gene encoding alcohol dehydrogenase deleted. Co-substrate yields were increased 2.3-fold and 2.4-fold, respectively, in these strains. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Applied Microbiology and Biotechnology
volume
59
issue
6
pages
641 - 648
publisher
Springer
external identifiers
  • wos:000178640000004
  • pmid:12226719
  • scopus:0036383398
ISSN
1432-0614
DOI
10.1007/s00253-002-1079-4
language
English
LU publication?
yes
id
44286f5b-e3a6-44e9-922a-7043ab072501 (old id 325808)
date added to LUP
2007-11-07 13:38:06
date last changed
2017-06-18 04:25:01
@article{44286f5b-e3a6-44e9-922a-7043ab072501,
  abstract     = {The stereoselective reduction of the bicyclic diketone bicyclo[2.2.2]octane-2,6-dione, to the ketoalcohol (1R,4S,6S)-6-hydroxybicyclo[2.2.2]octane-2-one, was used as a model reduction to optimize parameters involved in NADPH-dependent reductions in Saccharomyces cerevisiae with glucose as co-substrate. The co-substrate yield (ketoalcohol formed/glucose consumed) was affected by the initial concentration of bicyclic diketone, the ratio of yeast to glucose, the medium composition, and the pH. The reduction of 5 g l(-1) bicyclic diketone was completed in less than 20 h in complex medium (pH 5.5) under oxygen limitation with an initial concentration of 200 g l(-1) glucose and 5 g l(-1) yeast. The co-substrate yield was further enhanced by genetically engineered strains with reduced phosphoglucose isomerase activity and with the gene encoding alcohol dehydrogenase deleted. Co-substrate yields were increased 2.3-fold and 2.4-fold, respectively, in these strains.},
  author       = {Katz, Michael and Sarvary, Ian and Frejd, Torbjörn and Hahn-Hägerdal, Bärbel and Gorwa-Grauslund, Marie-Francoise},
  issn         = {1432-0614},
  language     = {eng},
  number       = {6},
  pages        = {641--648},
  publisher    = {Springer},
  series       = {Applied Microbiology and Biotechnology},
  title        = {An improved stereoselective reduction of a bicyclic diketone by Saccharomyces cerevisiae combining process optimization and strain engineering},
  url          = {http://dx.doi.org/10.1007/s00253-002-1079-4},
  volume       = {59},
  year         = {2002},
}