title: Cytosolic NADPH balancing in Penicillium chrysogenum cultivated on mixtures of glucose and ethanol.
abstract: The in vivo flux through the oxidative branch of the pentose phosphate pathway (oxPPP) in Penicillium chrysogenum was determined during growth in glucose/ethanol carbon-limited chemostat cultures, at the same growth rate. Non-stationary (13)C flux analysis was used to measure the oxPPP flux. A nearly constant oxPPP flux was found for all glucose/ethanol ratios studied. This indicates that the cytosolic NADPH supply is independent of the amount of assimilated ethanol. The cofactor assignment in the model of van Gulik et al. (Biotechnol Bioeng 68(6):602-618, 2000) was supported using the published genome annotation of P. chrysogenum. Metabolic flux analysis showed that NADPH requirements in the cytosol remain nearly the same in these experiments due to constant biomass growth. Based on the cytosolic NADPH balance, it is known that the cytosolic aldehyde dehydrogenase in P. chrysogenum is NAD(+) dependent. Metabolic modeling shows that changing the NAD(+)-aldehyde dehydrogenase to NADP(+)-aldehyde dehydrogenase can increase the penicillin yield on substrate.
authors.affiliation: Department of Biotechnology, Kluyver Centre for Genomics of Industrial Fermentation, Delft University of Technology, Julianalaan 67, 2628BC, Delft, The Netherlands. z.zhao@tudelft.nl
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhao
authors.forename: Karel
authors.initials: K
authors.lastname: Kuijvenhoven
authors.forename: Walter M
authors.initials: WM
authors.lastname: van Gulik
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Heijnen
authors.forename: Wouter A
authors.initials: WA
authors.lastname: van Winden
authors.forename: Peter J T
authors.initials: PJ
authors.lastname: Verheijen
mesh_terms: D003600:Cytosol / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010408:Penicillium chrysogenum / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D010427:Pentose Phosphate Pathway
chemical_list: D005656:Fungal Proteins; D000431:Ethanol; D009249:NADP; D005947:Glucose
references.citation: Metab Eng. 2006 Mar;8(2):91-101
references.pmid: 16253533
references.citation: J Biotechnol. 1996 Feb 28;45(2):149-64
references.pmid: 9147448
references.citation: FEMS Yeast Res. 2005 Apr;5(6-7):559-68
references.pmid: 15780655
references.citation: Appl Microbiol Biotechnol. 2007 May;75(1):47-53
references.pmid: 17216441
references.citation: Nat Prod Rep. 2000 Feb;17(1):85-97
references.pmid: 10714900
references.citation: Mol Gen Genet. 2001 Feb;264(6):755-62
references.pmid: 11254122
references.citation: Biotechnol Bioeng. 2008 Jul 1;100(4):734-43
references.pmid: 18383140
references.citation: Metab Eng. 2007 Jan;9(1):112-23
references.pmid: 17008114
references.citation: Nat Biotechnol. 2008 Oct;26(10):1161-8
references.pmid: 18820685
references.citation: Appl Microbiol Biotechnol. 1999 Aug;52(2):196-207
references.pmid: 10499259
references.citation: J Bacteriol. 1977 Jan;129(1):108-14
references.pmid: 12133
references.citation: Appl Environ Microbiol. 1994 Jun;60(6):1705-10
references.pmid: 8031073
references.citation: Appl Environ Microbiol. 2006 Jul;72(7):4743-54
references.pmid: 16820467
references.citation: Metab Eng. 2003 Jan;5(1):56-69
references.pmid: 12749845
references.citation: Appl Environ Microbiol. 2002 Dec;68(12):5843-59
references.pmid: 12450803
references.citation: FEBS Lett. 1979 Sep 15;105(2):333-6
references.pmid: 39785
references.citation: FEBS Lett. 1988 Dec 5;241(1-2):83-8
references.pmid: 2848727
references.citation: J Biol Chem. 1973 Mar 10;248(5):1848-55
references.pmid: 4348552
references.citation: J Biol Chem. 2005 Dec 2;280(48):39890-6
references.pmid: 16179340
references.citation: Biochim Biophys Acta. 1968 Apr 2;153(3):555-75
references.pmid: 4384979
references.citation: Biotechnol Bioeng. 2000 Jun 20;68(6):602-18
references.pmid: 10799985
references.citation: Genetics. 1966 Mar;53(3):609-19
references.pmid: 4380684
references.citation: Adv Biochem Eng Biotechnol. 2004;88:111-35
references.pmid: 15719554
references.citation: Appl Microbiol Biotechnol. 2008 Jun;79(3):471-9
references.pmid: 18379776
references.citation: Genome Biol. 2006;7(11):R108
references.pmid: 17107606
references.citation: Appl Environ Microbiol. 2004 Jan;70(1):229-39
references.pmid: 14711646
references.citation: Microbiology (Reading). 2008 Apr;154(Pt 4):1242-1250
references.pmid: 18375816
references.citation: Amino Acids. 2006 Mar;30(2):127-42
references.pmid: 16547652
references.citation: Appl Microbiol Biotechnol. 2003 Oct;62(5-6):459-67
references.pmid: 12845493
references.citation: Biotechnol Bioeng. 1994 Jan 5;43(1):3-10
references.pmid: 18613305
references.citation: J Bacteriol. 1987 Dec;169(12):5364-72
references.pmid: 2824433
references.citation: Metab Eng. 2008 Jan;10(1):10-23
references.pmid: 17905623
references.citation: Biochim Biophys Acta. 1971 Jul 20;244(1):129-34
references.pmid: 4399189
references.citation: Exp Eye Res. 2007 Jan;84(1):3-12
references.pmid: 16797007
references.citation: Mol Cell Biochem. 1983;51(2):123-7
references.pmid: 6343836
references.citation: Arch Biochem Biophys. 1971 Apr;143(2):617-63
references.pmid: 4397678
references.citation: Mol Gen Genet. 1998 Sep;259(5):549-56
references.pmid: 9790587
references.citation: Metab Eng. 2005 Jul;7(4):291-301
references.pmid: 15979917
references.citation: Biotechnol Bioeng. 2004 Feb 5;85(3):269-76
references.pmid: 14748081
references.citation: Annu Rev Biochem. 1983;52:537-79
references.pmid: 6137188
references.citation: Metab Eng. 2008 May-Jul;10(3-4):178-86
references.pmid: 18555197
references.citation: J Biol Chem. 2008 Jul 25;283(30):20621-7
references.pmid: 18364355
references.citation: Biochem Biophys Res Commun. 1990 Apr 30;168(2):837-43
references.pmid: 1970730
references.citation: Biophys J. 2007 Mar 1;92(5):1792-805
references.pmid: 17172310
references.citation: Funct Integr Genomics. 2009 May;9(2):167-84
references.pmid: 19156454
references.citation: Biochemistry. 1976 Sep 21;15(19):4191-07
references.pmid: 9133
references.citation: Eur J Biochem. 1972 May 23;27(2):301-17
references.pmid: 4340564
references.citation: J Gen Microbiol. 1971 Jul;67(1):85-90
references.pmid: 5001387
references.citation: J Gen Microbiol. 1983 Apr;129(4):965-71
references.pmid: 6684148
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713
references.citation: Microb Cell Fact. 2007 Nov 21;6:36
references.pmid: 18028553
references.citation: J Biol Chem. 1966 Jul 25;241(14):3430-4
references.pmid: 4380448
references.citation: J Biol Chem. 2003 Apr 18;278(16):13984-8
references.pmid: 12584194
references.citation: J Bacteriol. 1998 Jun;180(11):2875-82
references.pmid: 9603875
references.citation: Microbiology (Reading). 1997 Jan;143(1):253-257
references.pmid: 33711851