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Improving penicillin biosynthesis in Penicillium chrysogenum by glyoxalase overproduction.
- Source :
-
Metabolic engineering [Metab Eng] 2013 Jul; Vol. 18, pp. 36-43. Date of Electronic Publication: 2013 Apr 19. - Publication Year :
- 2013
-
Abstract
- Genetic engineering of fungal cell factories mainly focuses on manipulating enzymes of the product pathway or primary metabolism. However, despite the use of strong promoters or strains containing the genes of interest in multiple copies, the desired strongly enhanced enzyme levels are often not obtained. Here we present a novel strategy to improve penicillin biosynthesis by Penicillium chrysogenum by reducing reactive and toxic metabolic by-products, 2-oxoaldehydes. This was achieved by overexpressing the genes encoding glyoxalase I and II, which resulted in a 10% increase in penicillin titers relative to the control strain. The protein levels of two key enzymes of penicillin biosynthesis, isopenicillin N synthase and isopenicillin N acyltransferase, were increased in the glyoxalase transformants, whereas their transcript levels remained unaltered. These results suggest that directed intracellular reduction of 2-oxoaldehydes prolongs the functional lifetime of these enzymes.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Fungal Proteins genetics
Gene Dosage
Genetic Engineering methods
Lactoylglutathione Lyase genetics
Penicillium chrysogenum genetics
Penicillium chrysogenum growth & development
Fungal Proteins biosynthesis
Lactoylglutathione Lyase biosynthesis
Penicillins biosynthesis
Penicillium chrysogenum enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-7184
- Volume :
- 18
- Database :
- MEDLINE
- Journal :
- Metabolic engineering
- Publication Type :
- Academic Journal
- Accession number :
- 23608472
- Full Text :
- https://doi.org/10.1016/j.ymben.2013.04.003