Document Detail


Formate as an auxiliary substrate for glucose-limited cultivation of Penicillium chrysogenum: impact on penicillin G production and biomass yield.
MedLine Citation:
PMID:  17545326     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Production of beta-lactams by the filamentous fungus Penicillium chrysogenum requires a substantial input of ATP. During glucose-limited growth, this ATP is derived from glucose dissimilation, which reduces the product yield on glucose. The present study has investigated whether penicillin G yields on glucose can be enhanced by cofeeding of an auxiliary substrate that acts as an energy source but not as a carbon substrate. As a model system, a high-producing industrial strain of P. chrysogenum was grown in chemostat cultures on mixed substrates containing different molar ratios of formate and glucose. Up to a formate-to-glucose ratio of 4.5 mol.mol(-1), an increasing rate of formate oxidation via a cytosolic NAD(+)-dependent formate dehydrogenase increasingly replaced the dissimilatory flow of glucose. This resulted in increased biomass yields on glucose. Since at these formate-to-glucose ratios the specific penicillin G production rate remained constant, the volumetric productivity increased. Metabolic modeling studies indicated that formate transport in P. chrysogenum does not require an input of free energy. At formate-to-glucose ratios above 4.5 mol.mol(-1), the residual formate concentrations in the cultures increased, probably due to kinetic constraints in the formate-oxidizing system. The accumulation of formate coincided with a loss of the coupling between formate oxidation and the production of biomass and penicillin G. These results demonstrate that, in principle, mixed-substrate feeding can be used to increase the yield on a carbon source of assimilatory products such as beta-lactams.
Authors:
Diana M Harris; Zita A van der Krogt; Walter M van Gulik; Johannes P van Dijken; Jack T Pronk
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-01
Journal Detail:
Title:  Applied and environmental microbiology     Volume:  73     ISSN:  0099-2240     ISO Abbreviation:  Appl. Environ. Microbiol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-30     Completed Date:  2007-10-10     Revised Date:  2010-09-16    
Medline Journal Info:
Nlm Unique ID:  7605801     Medline TA:  Appl Environ Microbiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5020-5     Citation Subset:  IM    
Affiliation:
Delft University of Technology, Department of Biotechnology, Julianalaan 67, Delft, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Aerobiosis
Biomass*
Biotechnology / methods*
Culture Media
Formates / metabolism*
Glucose / metabolism*
Penicillin G / metabolism*
Penicillium chrysogenum / growth & development*,  metabolism
beta-Lactams / metabolism
Chemical
Reg. No./Substance:
0/Culture Media; 0/Formates; 0/beta-Lactams; 50-99-7/Glucose; 61-33-6/Penicillin G
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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