Scale-down of penicillin production in Penicillium chrysogenum

Biotechnology Journal

Volumn 6, Issue 8, 2011, Pages 944-958

  de Jonge, Lodewijk P ^a,b   Buijs, Nicolaas A A ^a,b   ten Pierick, Angela ^a   Deshmukh, Amit ^a   Zhao, Zheng ^a,b   Kiel, Jan A K W ^b,c   Heijnen, Joseph J ^a,b   van Gulik, Walter M ^a,b  

^a DELFT UNIVERSITY OF TECHNOLOGY   (Netherlands)

^b KLUYVER CENTRE FOR GENOMICS OF INDUSTRIAL FERMENTATION   (Netherlands)

^c UNIVERSITY OF GRONINGEN   (Netherlands)

Author keywords

Imperfect mixing; Industrial biotechnology; Intermittent feeding; Pulse feeding; Substrate concentration gradients

Indexed keywords

IMPERFECT MIXING; INDUSTRIAL BIOTECHNOLOGY; INTERMITTENT FEEDING; PULSE FEEDING; SUBSTRATE CONCENTRATION GRADIENTS;

ADENOSINETRIPHOSPHATE; BIOCHEMISTRY; CELL CULTURE; FEEDING; GLUCOSE; PHYSIOLOGY;

SUBSTRATES;

ADENOSINE PHOSPHATE; PENICILLIN G; PYROPHOSPHATE;

ANTIBIOTIC BIOSYNTHESIS; ARTICLE; BIOMASS; BIOMASS PRODUCTION; BIOREACTOR; CELL CULTURE; CELL FUNCTION; ENZYME SUBSTRATE; FUNGAL STRAIN; NONHUMAN; PENICILLIUM CHRYSOGENUM; PRIORITY JOURNAL; PROCESS DEVELOPMENT;

CARBON CYCLE; COENZYME A LIGASES; GLUCOSE; INDUSTRIAL MICROBIOLOGY; METABOLIC NETWORKS AND PATHWAYS; OXIDOREDUCTASES; PENICILLINS; PENICILLIUM CHRYSOGENUM; PEPTIDE SYNTHASES;

PENICILLIUM CHRYSOGENUM;

EID: 79961188551     PISSN: 18606768     EISSN: 18607314     Source Type: Journal    
DOI: 10.1002/biot.201000409     Document Type: Article

References (53)

1. Galaction, A. I., Cascaval, D., Oniscu, C., Turnea, M., Evaluation and modeling of the aerobic stirred bioreactor performances for fungus broths. Chem. Biochem. Eng. Q. 2005, 19, 87-97.
2. Jansen, P. H., Slott, S., Gürtler, H., Determination of mixing times in large-scale fermentors using radioactive isotopes. Preprints of the 1st European Congress on Biotechnology, 1978, 80-82.
3. Marten, M. R., Wenger, K. S., Kahn, S. A., Rheology, mixing time, and regime analysis for a production-scale Aspergillus oryzae fermentation. Proceedings of the 4th International Conference in Bioreactor & Bioprocess Fluid Dynamics 1997, 295-313.
4. Pollard, D. J., Kirschner, T. F., Hunt, G. R., Tong, I. T. et al., Scale up of a viscous fungal fermentation: Application of scale-up criteria with regime analysis and operating boundary conditions. Biotechnol. Bioeng. 2007, 96, 307-317.
5. Larsson, G., Tornkvist, M., Wernersson, E. S., Tragardh, C. et al., Substrate gradients in bioreactors: Origin and consequences. Bioprocess Eng. 1996, 14, 281-289.
6. Bylund, F., Collet, E., Enfors, S. O., Larsson, G., Substrate gradient formation in the large-scale bioreactor lowers cell yield and increases by-product formation. Bioprocess Eng. 1998, 18, 171-180.
7. Langheinrich, C., Nienow, A. W., Control of pH in large-scale, free suspension animal cell bioreactors: Alkali addition and pH excursions. Biotechnol. Bioeng. 1999, 66, 171-179.
8. Oosterhuis, N. M. G., Kossen, N. W. F., Dissolved-oxygen concentration profiles in a production-scale bioreactor. Biotechnol. Bioeng. 1984, 26, 546-550.
9. Lara, A. R., Galindo, E., Ramirez, O. T., Palomares, L. A., Living with heterogeneities in bioreactors. Mol. Biotechnol. 2006, 34, 355-381.
10. Neubauer, P., Junne, S., Scale-down simulators for metabolic analysis of large-scale bioprocesses. Curr. Opin. Biotechnol. 2010, 21, 114-121.
11. Van Kleeff, B. H. A., Kuenen, J. G., Heijnen, J. J., Heat flux measurements for the fast monitoring of dynamic responses to glucose additions by yeasts that were subjected to different feeding regimes in continuous culture. Biotechnol. Prog. 1996, 12, 510-518.
12. Sweere, A. P. J., Matla, Y. A., Zandvliet, J., Luyben, K. Ch. A. M. et al., Experimental simulation of glucose fluctuations. Appl. Microbiol. Biotechnol. 1988, 28, 109-115.
13. George, S., Larsson, G., Enfors, S. O., A scale-down two-compartment reactor with controlled substrate oscillations: Metabolic response of Saccharomyces cerevisiae. Bioprocess Eng. 1993, 9, 249-257.
14. Visser, D., van Zuylen, G. A., van Dam, J. C., Oudshoorn, A. et al., Rapid sampling for analysis of in vivo kinetics using the BioScope: A system for continuous-pulse experiments. Biotechnol. Bioeng. 2002, 79, 674-681.
15. Mashego, M. R., van Gulik, W. M., Vinke, J. L., Visser, D. et al., In vivo kinetics with rapid perturbation experiments in Saccharomyces cerevisiae using a second-generation BioScope. Metab. Eng. 2006, 8, 370-383.
16. Voncken, R. M., Holmes, D. B., Denhartog, H. W., Fluid flow in turbine-stirred, baffled tanks-II. Dispersion during circulation. Chem. Eng. Sci. 1964, 19, 209-213.
17. Kresse, H., Belsey, M. J., Rovini, H., The antibacterial drugs market. Nat. Rev. Drug Discovery 2007, 6, 19-20.
18. Schmidt, F. R., The beta-lactam Antibiotics: Current Situation and Future Prospects in Manufacture and Therapy, in: Hofrichter, M. (Ed.), Industrial Applications X, Springer, Heidelberg 2010, pp. 101-12.
19. Larsson, G., Enfors, S. O., Studies of insufficient mixing in bioreactors-effects of limiting oxygen concentrations and short-term oxygen starvation on Penicillium chrysogenum. Bioprocess Eng. 1988, 3, 123-127.
20. Vardar, F., Lilly, M. D., Effect of cycling dissolved-oxygen concentrations on product formation in penicillin fermentations. Eur. J. Appl. Microbiol. Biotechnol. 1982, 14, 203-211.
21. Henriksen, C. M., Nielsen, J., Villadsen, J., Influence of the dissolved oxygen concentration on the penicillin biosynthetic pathway in steady-state cultures of Penicillium chrysogenum. Biotechnol. Prog. 1997, 13, 776-782.
22. Harris, D. M., Diderich, J. A., van der Krogt, Z. A., Luttik, M. A. H. et al., Enzymic analysis of NADPH metabolism in beta-lactam-producing Penicillium chrysogenum: Presence of a mitochondrial NADPH dehydrogenase. Metab. Eng. 2006, 8, 91-101.
23. Douma, R. D., de Jonge, L. P., Jonker, C. T. H., Seifar, R. M. et al., Intracellular metabolite determination in the presence of extracellular abundance: Application to the penicillin biosynthesis pathway in Penicillium chrysogenum. Biotechnol. Bioeng. 2010, 107, 105-115.
24. van Gulik, W. M., De Laat, W. T. A. M., Vinke, J. L., Heijnen, J. J., Application of metabolic flux analysis for the identification of metabolic bottlenecks in the biosynthesis of penicillin-G. Biotechnol. Bioeng. 2000, 68, 602-618.
25. Zhao, Z., Kuijvenhoven, K., Ras, C., van Gulik, W. M. et al., Isotopic non-stationary C-13 gluconate tracer method for accurate determination of the pentose phosphate pathway split-ratio in Penicillium chrysogenum. Metab. Eng. 2008, 10, 178-186.
26. Christensen, L. H., Mandrup, G., Nielsen, J., Villadsen, J., A robust liquid-chromatographic method for measurement of medium components during penicillin fermentations. Anal. Chim. Acta 1994, 296, 51-62.
27. Mashego, M. R., van Gulik, W. M., Vinke, J. L., Heijnen, J. J., Critical evaluation of sampling techniques for residual glucose determination in carbon-limited chemostat culture of Saccharomyces cerevisiae. Biotechnol. Bioeng. 2003, 83, 395-399.
28. Nasution, U., van Gulik, W. M., Kleijn, R. J., Van Winden, W. A. et al., Measurement of intracellular metabolites of primary metabolism and adenine nucleotides in chemostat cultivated Penicillium chrysogenum. Biotechnol. Bioeng. 2006, 94, 159-166.
29. Seifar, R. M., Ras, C., van Dam, J. C., van Gulik, W. M. et al., Simultaneous quantification of free nucleotides in complex biological samples using ion pair reversed phase liquid chromatography isotope dilution tandem mass spectrometry. Anal. Biochem. 2009, 388, 213-219.
30. Seifar, R. M., Zhao, Z., van Dam, J., van Winden, W. et al., Quantitative analysis of metabolites in complex biological samples using ion-pair reversed-phase liquid chromatography-isotope dilution tandem mass spectrometry. J. Chromatogr. A 2008, 1187, 103-110.
31. Cipollina, C., ten Pierick, A., Canelas, A. B., Seifar, R. M. et al., A comprehensive method for the quantification of the non-oxidative pentose phosphate pathway intermediates in Saccharomyces cerevisiae by GC-IDMS. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2009, 877, 3231-3236.
32. Mashego, M. R., Wu, L., van Dam, J. C., Ras, C. et al., MIRACLE: Mass isotopomer ratio analysis of U-C-13-labeled extracts. A new method for accurate quantification of changes in concentrations of intracellular metabolites. Biotechnol. Bioeng. 2004, 85, 620-628.
33. Wu, L., Mashego, M. R., van Dam, J. C., Proell, A. M. et al., Quantitative analysis of the microbial metabolome by isotope dilution mass spectrometry using uniformly C-13-labeled cell extracts as internal standards. Anal. Biochem. 2005, 336, 164-171.
34. Kiel, J. A. K. W., van den Berg, M. A., Fusetti, F., Poolman, B. et al., Matching the proteome to the genome: the microbody of penicillin-producing Penicillium chrysogenum cells. Funct. Integr. Genomics 2009, 9, 167-184.
35. Nasution, U., van Gulik, W. M., Ras, C., Proell, A. et al., A metabolome study of the steady-state relation between central metabolism, amino acid biosynthesis and penicillin production in Penicillium chrysogenum. Metab. Eng. 2008, 10, 10-23.
36. Christensen, L. H., Henriksen, C. M., Nielsen, J., Villadsen, J. et al., Continuous cultivation of Penicillium chrysogenum-growth on glucose and penicillin production. J. Biotechnol. 1995, 42, 95-107.
37. Righelato, R. C., Selection of strains of Penicillium chrysogenum with reduced penicillin yields in continuous cultures. J. Appl. Chem. Biotechnol. 1976, 26, 153-159.
38. Rodriguez-Saiz, M., Barredo, J. L., Moreno, M. A., Fernandez-Canon, J. M. et al., Reduced function of a phenylacetate-oxidizing cytochrome P450 caused strong genetic improvement in early phylogeny of penicillin-producing strains. J. Bacteriol. 2001, 183, 5465-5471.
39. Harris, D. M., van der Krogt, Z. A., Klaassen, P., Raamsdonk, L. M. et al., Exploring and dissecting genome-wide gene expression responses of Penicillium chrysogenum to phenylacetic acid consumption and penicillinG production. BMC Genomics 2009, 10, 75.
40. Feng, B., Friedlin, E., Marzluf, G. A., A reporter gene analysis of penicillin biosynthesis gene expression in Penicillium chrysogenum and its regulation by nitrogen and glucose catabolite repression. Appl. Environ. Microbiol. 1994, 60, 4432-4439.
41. van Gulik, W. M., Antoniewicz, M. R., Delaat, W. T. A. M., Vinke, J. L. et al., Energetics of growth and penicillin production in a high-producing strain of Penicillium chrysogenum. Biotechnol. Bioeng. 2001, 72, 185-193.
42. Nasution, U., van Gulik, W. M., Proell, A., Van Winden, W. A. et al., Generating short-term kinetic responses of primary metabolism of Penicillium chrysogenum through glucose perturbation in the bioscope mini reactor. Metab. Eng. 2006, 8, 395-405.
43. Brakhage, A. A., Sprote, P., Al-Abdallah, Q., Gehrke, A. et al., Regulation of penicillin biosynthesis in filamentous fungi. Adv. Biochem. Eng. Biotechnol. 2004, 88, 45-90.
44. Martin, J. E., Casqueiro, J., Kosalkova, K., Marcos, A. T. et al., Penicillin and cephalosporin biosynthesis: Mechanism of carbon catabolite regulation of penicillin production. Antonie Van Leeuwenhoek 1999, 75, 21-31.
45. Bartoszewska, M., Kiel, J. A. K. W., Bovenberg, R. A. L., Veenhuis, M. et al., Autophagy deficiency promotes beta-lactam production in Penicillium chrysogenum. Appl. Environ. Microbiol. 2011, 77, 1413-1422.
46. Pollack, J. K., Harris, S. D., Marten, M. R., Autophagy in filamentous fungi. Fungal Genet. Biol. 2009, 46, 1-8.
47. Hillenga, D. J., Versantvoort, H. J. M., Vandermolen, S., Driessen, A. J. M. et al., Penicillium chrysogenum takes up the penicillin-G precursor phenylacetic acid by passive diffusion. Appl. Environ. Microbiol. 1995, 61, 2589-2595.
48. van den Berg, M. A., Bovenberg, R. A. L., Driessen, A. J. M., Konings, W. N. et al., Method for enhancing secretion of beta-lactam transport. PCT patent WO2001/32904, 2001.
49. Nijland, J. G., Ebbendorf, B., Woszczynska, M., Boer, R. et al., Nonlinear biosynthetic gene cluster dose effect on penicillin production by Penicillium chrysogenum. Appl. Environ. Microbiol. 2010, 76, 7109-7115.
50. Revilla, G., Lopeznieto, M. J., Luengo, J. M., Martin, J. F., Carbon catabolite Repression of penicillin biosynthesis by Penicillium chrysogenum. J. Antibiot. 1984, 37, 781-789.
51. Theilgaard, H. B. A., Kristiansen, K. N., Henriksen, C. M., Nielsen, J., Purification and characterization of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase from Penicillium chrysogenum. Biochem. J. 1997, 327, 185-191.
52. Jaklitsch, W. M., Hampel, W., Rohr, M., Kubicek, C. P. et al., alpha-Aminoadipate pool concentration and penicillin biosynthesis in strains of Penicillium chrysogenum. Can. J. Microbiol. 1986, 32, 473-480.
53. Zhang, J. Y., Wolfe, S., Demain, A. L., Biochemical studies on the activity of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase from Streptomyces clavuligerus. Biochem. J. 1992, 283, 691-698.