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Strain engineering for stereoselective bioreduction of dicarbonyl compounds by yeast reductases

Johanson, Ted LU ; Katz, Michael LU and Gorwa-Grauslund, Marie-Francoise LU (2005) In FEMS Yeast Research 5(6-7). p.513-525
Abstract
Pure chiral molecules are needed in the pharmaceutical and chemical industry as intermediates for the production of drugs or fine chemicals. Microorganisms represent an attractive alternative to chemical synthesis since they have the potential to generate single stereoisomers in high enantiomeric excess (ee). The baker's yeast Saccharomyces cerevisiae can notably reduce dicarbonyl compounds (in particular alpha- and beta-diketones and keto esters) to chiral alcohols with high ee. However, products are formed at a low rate. Moreover, large amounts of co-substrate are required for the regeneration of NADPH that is the preferred co-factor in almost all the known dicarbonyl reductions. Traditionally, better ee, reduction rate and product titre... (More)
Pure chiral molecules are needed in the pharmaceutical and chemical industry as intermediates for the production of drugs or fine chemicals. Microorganisms represent an attractive alternative to chemical synthesis since they have the potential to generate single stereoisomers in high enantiomeric excess (ee). The baker's yeast Saccharomyces cerevisiae can notably reduce dicarbonyl compounds (in particular alpha- and beta-diketones and keto esters) to chiral alcohols with high ee. However, products are formed at a low rate. Moreover, large amounts of co-substrate are required for the regeneration of NADPH that is the preferred co-factor in almost all the known dicarbonyl reductions. Traditionally, better ee, reduction rate and product titre have been achieved via process engineering. The advent of recombinant DNA technology provides an alternative strategy to improve productivity and yield by strain engineering. This review discusses two aspects of strain engineering: (i) the generation of strains with higher reductase activity towards dicarbonyl compounds and (ii) the optimisation of co-substrate utilisation for NADPH cofactor regeneration. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
FEMS Yeast Research
volume
5
issue
6-7
pages
513 - 525
publisher
Elsevier
external identifiers
  • wos:000228153900003
  • pmid:15780652
  • scopus:15044350989
ISSN
1567-1364
DOI
10.1016/j.femsyr.2004.12.006
language
English
LU publication?
yes
id
27cfbfbc-824a-42a6-b356-0080ce8ca6ea (old id 151261)
date added to LUP
2007-06-28 13:47:22
date last changed
2017-01-15 03:26:31
@article{27cfbfbc-824a-42a6-b356-0080ce8ca6ea,
  abstract     = {Pure chiral molecules are needed in the pharmaceutical and chemical industry as intermediates for the production of drugs or fine chemicals. Microorganisms represent an attractive alternative to chemical synthesis since they have the potential to generate single stereoisomers in high enantiomeric excess (ee). The baker's yeast Saccharomyces cerevisiae can notably reduce dicarbonyl compounds (in particular alpha- and beta-diketones and keto esters) to chiral alcohols with high ee. However, products are formed at a low rate. Moreover, large amounts of co-substrate are required for the regeneration of NADPH that is the preferred co-factor in almost all the known dicarbonyl reductions. Traditionally, better ee, reduction rate and product titre have been achieved via process engineering. The advent of recombinant DNA technology provides an alternative strategy to improve productivity and yield by strain engineering. This review discusses two aspects of strain engineering: (i) the generation of strains with higher reductase activity towards dicarbonyl compounds and (ii) the optimisation of co-substrate utilisation for NADPH cofactor regeneration. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.},
  author       = {Johanson, Ted and Katz, Michael and Gorwa-Grauslund, Marie-Francoise},
  issn         = {1567-1364},
  language     = {eng},
  number       = {6-7},
  pages        = {513--525},
  publisher    = {Elsevier},
  series       = {FEMS Yeast Research},
  title        = {Strain engineering for stereoselective bioreduction of dicarbonyl compounds by yeast reductases},
  url          = {http://dx.doi.org/10.1016/j.femsyr.2004.12.006},
  volume       = {5},
  year         = {2005},
}