1887

Chapter 60 : Fermentation of Bacillus

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

Fermentation of Bacillus, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818388/9781555810535_Chap60-1.gif /docserver/preview/fulltext/10.1128/9781555818388/9781555810535_Chap60-2.gif

Abstract:

The products in commerce today that are produced by fermentations include enzymes antibiotics , and insecticides. This chapter focuses on the basic principles necessary for an understanding of growth and product production in spp. The authors show the important link between some very basic observations and how these can be (and need to be) applied in medium development processes, choice of equipment, and elimination of bottlenecks in production. Using protease production as a model, examples show the potential value of using controlled fermentations in identifying some of the limitations of product formation in spp. spp. as a class are known to secrete a large number of extracellular enzymes, including several proteases , amylase, cellulase, and other degradative enzymes. Costs of exoprotein production can be estimated from material balances, molecular formulae, and growth parameters. Results of these calculations can be a key element in choosing a fermentor type and mode of operation for desired product formation. The functions included under strain development are identification and isolation of an organism exhibiting the trait (or traits) of interest; analysis and optimization of cultural conditions that allow expression of the trait; and mutagenesis, selection, and screening for isolates that hyperproduce the trait. In addition, overexpression of these proteins may improve the secretion efficiency of heterologous proteins, as has been demonstrated for signal peptidase.

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60

Key Concept Ranking

Chemicals
0.5271926
Bacterial Growth
0.46709988
Microbial Growth Kinetics
0.45123518
Bacillus licheniformis
0.4309918
0.5271926
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

Main characteristics of predominant fermentor types. Many variations on these archetypes are possible (e.g., the feed rate in an FB need not be constant). volume of culture; c, constant, specific growth rate; x, biomass. (A) Batch fermentor (BcSc). Nutrient is present from the beginning; no feed. No steady state can be reached. (B) FB (BcSc). Nutrient is fed at a constant or variable rate; there is (usually) no flow out of the fermentor. As described in the text, growth in a carbon-limited FB can initially proceed exponentially (domain 1), after which (at least) one domain (domain 2) of linear growth occurs. No steady state can be reached. (C) CF, e.g., chemostat (BoSo). Nutrient is fed at a constant rate. Rate of inflow (F) equals rate of outflow (Fo); dilution rate In steady state, (D) Combination of fermentor types. If inflow equals outflow (Fo) while the filtrate flow (Ff) equals 0, this type is, again, a chemostat with = c, and If Ff > 0 and Fo = 0, then D1 is a 100% RF (BcSo). Nutrient is fed at a constant rate. Rate of inflow (F) equals rate of filtrate-flow (Ff). Culture broth is continuously recycled over a cell separation unit (e.g., filter), biomass is returned to the fermentor, and filtrate is pumped off. No steady state can be reached. If Ff > 0 and Fo > 0, then D2 is a PRF (BoSo). = c. As in the 100% RF, culture broth is continuously recycled over a cell separation unit. Not as in the RF, here Ff < F; part of the culture broth is pumped off at rate Fo; so, F = (Ff + Fo). In fact, a PRF is a CF type like the chemostat; here, too, = c, but Fo/V ≠ (the Fo of a PRF is usually referred to as “bleed” [], so Nutrient is fed at a constant rate, and a steady state can be reached.

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Dependence of growth yield []on reduction degree of substrate (A) and relative differences in free energies of substrate, biomasses, and exoproducts (B). (A) Growth on a substrate with 4 tends to be carbon limited and energy sufficient; for 4, the reverse will hold. Initially 4), the increase in free-energy content of the substrate is reflected in an increase in biomass yield ( ). Above a certain (about 4 to 4.5), ATP yield from the substrate can exceed ATP demands for biomass synthesis, and in order to sustain high metabolic rates, this surplus needs to be turned over by energy-spilling reactions (including energy-requiring exoproduct formation) (see text). (B) The free-energy content of, e.g., citrate is lower than that of biomass; bridging that gap is obtained by combusting a significant portion of the substrate to CO and HO to produce energy. Concomitant synthesis of exoproduct 2 is possible; that of exoproduct 1 is very unlikely. At growth on, e.g., ethanol, a surplus of free energy that could be shunted toward synthesis of both exoproducts 1 and 2 will be available. Glucose 4) holds an intermediate position among these substrates, with a very close to (=4.2). Obviously, simultaneous consumption of two substrates with different values could also be a means of steering carbon and energy flows toward a more-desirable product formation than is possible with one substrate only. These schemes should be regarded in relation to biochemical routes. Growth on methanol, for instance, has been found to be energy limited despite the high of methanol. This was due to the occurrence of CO fixation via the costly Calvin cycle ( ). For that type of growth, the substrate is actually not methanol but methanol + CO, with a lower than for methanol, (idealized drawing in panel A is based on one in reference ; reduction degrees are as defined in reference ).

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Theoretical exoproduct formation in batch (A) and fed batch (B) cultures. In panel A, five strains are evaluated for exoproduct formation by using batch cultures (i.e., screening stage). The same five strains are run in a carbon-limited fed-batch culture (i.e., production stage) (B). The production profiles show how the amounts of product in batch cultures at any time of sampling (without knowing the and values in equation 22) cannot lead to reliable predictions of exoproduct formation in fed-batch cultures. For further discussion, see text. Assumptions are that in the batch culture, growth of all five strains halted after consumption of 50 mmol of glucose because a compound other than the carbon and nitrogen source became limited. Growth in the fed-batch culture proceeded glucose limited (constant feed rate [ ] = 0.001 mol/[g · ])Exoproduct formation is described by ( ). The value of (in grams per gram · hour) is constant; (in grams per gram) was assumed to be described as follows: 1, = 0.117 - 0.14μ; 2, = 0.530 - 0.83μ; 3, = 0.530 - 0.80μ; 4, = 0.117 - 0.10μ; 5, = 0.117 - 0.07μ (relations that can be obtained from, e.g., chemostat experiments). Other parameter values: = 1 liter; =100 g/mol; = 60 g/mol; = 0.00024 mol/(g · h); = 0.01 g (A) or 0.5 g (B); 0 g (calculated according to van Verseveld et al. [ ]; values for strains 2 through 5 in panel ? are from that publication but modified).

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Exoprotease enzyme activity levels and respiration rate in a glucose fed-batch fermentation of ( ). (A) Wild type ( ); (B) mutant. OUR, oxygen uptake rate.

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Trend of rates of production versus respiration rates. OUR, oxygen uptake rate.

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6
Figure 6

Total protein synthesis and secreted protein synthesis as measured by [S]methionine counts in a glucose fed-batch fermentation of

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 7
Figure 7

Percentage of secreted protein synthesis as measured by [S]methionine counts in glucose fed-batch fermentation of

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 8
Figure 8

Relative mRNA levels versus exoprotease levels in a glucose fed-batch fermentation of ( ).

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555818388.chap60
1. Anonymous. 1990. Biotechnologies and food: assuring the safety of foods produced by genetic modification. Regul. Toxicol. Pharmacol. 12(Part 2):1196.
2. Arbige, M.,, and W. R. Chesbro. 1982. Very slow growth of Bacillus polymyxa: stringent response and maintenance energy. Arch. Microbiol. 132:338344.
3. Arbige, M.,, and W. R. Chesbro. 1982. relA and related loci are growth rate determinants for Escherichia coli in a recycling fermentor. J. Gen. Microbiol. 128:693703.
4. Arbige, M. V.,, and W. H. Pitcher. 1989. Industrial enzymology: a look towards the future. Trends Biotechnol. 7:330335.
5. Babel, W.,, and R. H. Müller. 1985. Correlation between cell composition and carbon conversion efficiency in microbial growth: a theoretical study. Appl. Microbiol. Biotechnol. 22:201207.
6. Babel, W.,, and H. W. van Verseveld,. 1987. Theoretical limits of growth yields and an analysis of experimental data, p. 210219. In H. W. van Verseveld, and J. A. Duine (ed.), Microbial Growth on CI Compounds. Martinus Nijhoff Publishers, Dordrecht, The Netherlands.
7. Bailey, J. E., 1983. Single-cell metabolic model determination by analysis of microbial populations, p. 135157. In H. W. Blanch,, E. T. Papoutsakis,, and G. Stephanopoulos (ed.). Foundations of Biochemical Engineering. Kinetics and Thermodynamics in Biological Systems. ACS symposium series 207. American Chemical Society, Washington, D.C.
8. Baloo, S.,, and D. Ramkrishna. 1991. Metabolic regulation in bacterial continuous cultures. II. Biotechnol. Bioeng. 38:13531363.
9. Baloo, S.,, and D. Ramkrishna. 1991. Metabolic regulation in bacterial continuous cultures. I. Biotechnology 12:13371352.
10. Baltzis, B. C.,, and A. G. Frederickson. 1988. Limitation of growth rate by two complementary nutrients: some elementary but neglected considerations. Biotechnol. Bioeng. 31:7586.
11. Basalp, A.,, G. Ozcengiz,, and N. G. Alaeddlnoglu. 1992. Changes in patterns of alkaline serine protease and bacilysin formation caused by common effectors of sporulation in Bacillus subtilis 168. Curr. Microbiol. 24:129135.
12. Bazln, M.,, S. Gray,, and E. Rashit,. 1990. Stability properties of microbial populations, p. 127143. In R. K. Poole,, M. J. Bazin,, and W. Keevil (ed.), Microbial Growth Dynamics. Society for General Microbiology special publication 28. IRL Press, Oxford.
13. Behal, V. 1986. Enzymes of secondary metabolism in microorganisms. Trends Biochem. Sci. 11:8891.
14. Bella, L. A.,, R. M. Faust,, R. Andrews,, and N. Goodman,. 1985. Insecticidal bacilli, p. 186210. In D. Dubnau (ed.). Molecular Biology of the Bacilli, vol. 2. Academic Press, Inc., Orlando, Fla.
15. Bley, T.,, and W. Babel. 1992. Calculating affinity constants of substrate mixtures in a chemostat. Acta Biotechnol. 12:1315.
16. Boon, B.,, and H. Laudelot. 1962. Kinetics of nitrite oxidation by Nitrobacter winogradsky. Biochem. J. 85: 440447.
17. Both, G. W.,, J. L. Mclnnes,, J. E. Hanlon,, B. K. May,, and W. H. Elliott. 1972. Evidence for an accumulation of messenger RNA specific for extracellular protease and its relevance to the mechanism of enzyme secretion in bacteria. J. Mol. Biol. 67:199217.
18. Bremer, H.,, and P. P. Dennis,. 1987. Modulation of chemical composition and other parameters of the cell by growth rate, p. 15271542. In F. C. Neidhardt,, J. L. Ingraham,, K. B. Low,, B. Magasanik,, M. Schaechter,, and H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology, vol. 2. American Society for Microbiology, Washington, D.C.
19. Brooks, J. D.,, and J. L. Meers. 1973. The effect of discontinuous methanol addition on the growth of a C-limited culture of Pseudomonas. J. Gen. Microbiol. 77:513519.
20. Bull, A. T., 1974. Microbial growth, p. 415442. In A. T. Bull,, J. R. Lagnado,, J. O. Thomas,, and K. F. Tipton (ed.), Companion to Biochemistry. Longman, London.
21. Bull, A. T.,, M. E. Bushell,, T. G. Mason,, and J. H. Slater. 1975. Growth of filamentous fungi in batch culture: a comparison of the Monod and logistic models. Proc. Soc. Gen. Microbiol. 3:6263.
22. Bulthuis, B. A. 1990. Stoichiometry of growth and product-formation by Bacillus licheniformis. Ph.D. thesis. Free University, Amsterdam, The Netherlands.
23. Bulthuis, B. A.,, J. Frankena,, G. M. Koningstein,, A. H. Stouthamer,, and H. W. van Verseveld. 1988. Instability of protease production in a rel*/rel~-pair of Bacillus licheniformis and associated morphological and physiological characteristics. Antonie van Leeuwenhoek Int. J. Gen. Mol. Microbiol. 54:95111.
24. Bulthuis, B. A.,, G. M. Koningstein,, A. H. Stouthamer,, and H. W. van Verseveld. 1989. A comparison between aerobic growth of Bacillus licheniformis in continuous culture and partial-recycling fermentor, with contributions to the discussion on maintenance energy demand. Arch. Microbiol. 152:499507.
25. Bulthuis, B. A.,, C. Rommens,, G. M. Koningstein,, A. H. Stouthamer,, and H. W. van Verseveld. 1991. Formation of fermentation products and extracellular protease during anaerobic growth of Bacillus licheniformis in chemostat and batch-culture. Antonie van Leeuwenhoek Int. J. Gen. Mol. Microbiol. 60:355371.
26. Cashel, M.,, and K. E. Rudd,. 1987. The stringent response, p. 14101438. In F. C. Neidhardt,, J. L. Ingraham,, K. B. Low,, M. Schaechter,, and H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology, vol. 2. American Society for Microbiology, Washington, D.C.
27. Charles, M., 1985. Fermentor design and scale-up, p. 5775. In C. L. Cooney, and A. E. Humphrey (ed.), Comprehensive Biotechnology; the Principles, Applications and Regulations of Biotechnology in Industry, Agriculture and Medicine, vol. 2. Pergamon Press, Oxford.
28. Chesbro, W. R.,, M. Arbige,, and R. Eifert. 1990. When nutrient limitation places bacteria in the domains of slow growth: metabolic, morphologic and cell cycle behavior. FEMS Microbiol. Ecol. 74:103120.
29. Chesbro, W. R.,, T. Evans,, and R. Eifert. 1979. Very slow growth of Escherichia coli. J. Bacteriol. 139:625638.
30. Crabb, W. D., 1990. Subtilisin: a commercially relevant model for large-scale enzyme production, p. 8294. In G. F. Leatham, and M. Himmel (ed.), Enzymes in Biomass Conversion. American Chemical Society, Washington, D.C.
31. Dabes, J. N.,, R. K. Finn,, and C. R. Wilke. 1973. Equations of substrate limited growth: the case for Blackman kinetics. Biotechnol. Bioeng. 15:11591177.
32. Dawes, E. A.,, D. J. McGill,, and M. Midgley. 1971. Analysis of fermentation products. Methods Microbiol. 6:53217.
33. Demain, A. L., 1987. Production of nucleotides by microorganisms, p. 178208. In A. H. Rose (ed.). Economic Microbiology, vol. 2. Primary Products of Metabolism, Academic Press, London.
34. Dhurjati, P.,, D. Ramkrishna,, M. C. Flickinger,, and G. T. Tsao. 1985. A cybernetic view of microbial growth: modelling of cells as optimal strategists. Biotechnol. Bioeng. 27:19.
35. Domach, M. M.,, S. K. Leung,, R. E. Cahn,, G. G. Cocks,, and M. L. Shuler. 1984. Computer model for glucose-limited growth of a single cell of Escherichia coli B/r-A. Biotechnol. Bioeng. 26:203216.
36. Domach, M. M.,, and M. L. Shuler. 1984. A finite representation model for an asynchronous culture of E. coli. Biotechnol. Bioeng. 26:877884.
37. Egli, T. 1991. On multiple-nutrient-limited growth of microorganisms, with special reference to dual limitation by carbon and nitrogen substrates. Antonie van Leeuwenhoek Int. J. Gen. Mol. Microbiol. 60:225334.
38. Ellwood, D. C.,, and D. W. Tempest. 1972. Effects of environment on bacterial wall content and composition. Adv. Microb. Physiol. 7:83117.
39. Erickson, L. E.,, I. G. Minkevich,, and V. K. Eroshin. 1978. Application of mass and energy balance regularities in fermentation. Biotechnol. Bioeng. 20:15951621.
40. Esener, A. A.,, J. A. Roels,, and N. W. F. Kossen. 1981. Fed-batch culture: modelling and applications in the study of microbial energetics. Biotechnol. Bioeng. 23:18511871.
41. Esener, A. A.,, J. A. Roels,, and N. W. F. Kossen. 1983. Theory and applications of unstructured growth models: kinetic and energetic aspects. Biotechnol. Bioeng. 25:28032841.
42. Esener, A. A.,, T. Veerman,, J. A. Roels,, and N. W. F. Kossen. 1982. Modelling of bacterial growth; formulation and evaluation of a structured model. Biotechnol. Bioeng. 24:17491764.
43. Feitelson, J. S.,, J. Payne,, and L. Kim. 1992. Bacillus thuringiensis: insects and beyond. Bio/Technology 10: 271275.
44. Fencl, Z.,, J. Ricica,, and J. Kodesova. 1972. The use of the multi-stage chemostat for microbial product formation. J. Appl. Chem. Biotechnol. 22:405416.
45. Ferrari, E.,, H. Heinsohn,, B. Christensen,, J. Schultz,, B. A. Bulthuis,, D. Crabb,, and M. Arbige. 1991. Biochemical changes during subtilisin production in Bacillus subtilis. Abstr. 6th Int. Conf. Bacilli, Stanford, Calif.
46. Ferrari, E.,, D. J. Henner,, M. Perego,, and J. A. Hoch. 1988. Transcription of Bacillus subtilis subtilisin and expression of subtilisin in sporulation mutants. J. Bacteriol. 170:289295.
47. Ferrari, E.,, S. M. H. Howard,, and J. A. Hoch,. 1985. Effect of sporulation mutations on subtilisin expression, assayed using a subtilisin-beta-galactosidase gene fusion, p. 180184. In J. A. Hoch, and P. Setlow (ed.), Molecular Biology of Microbial Differentiation. American Society for Microbiology, Washington, D.C.
48. Fisher, S. H.,, and A. L. Sonnenshein. 1991. Control of carbon and nitrogen metabolism in Bacillus subtilis. Annu. Rev. Microbiol. 45:105135.
49. Frankena, J.,, G. M. Koningstein,, H. W. van Verseveld,, and A. H. Stouthamer. 1986. Effect of different limitations in chemostat cultures on growth and production of exocellular protease by Bacillus licheniformis. Appl. Microbiol. Biotechnol. 24:106112.
50. Frankena, J.,, H. W. van Verseveld,, and A. H. Stouthamer. 1985. A continuous culture study of the bioenergetic aspects of growth and production of exocellular protease in Bacillus licheniformis. Appl. Microbiol. Biotechnol. 22:169176.
51. Frankena, J.,, H. W. van Verseveld,, and A. H. Stouthamer. 1988. Substrate and energy costs of the production of exocellular enzymes by Bacillus licheniformis. Biotechnol. Bioeng. 32:803812.
52. Gottschal, J. C. 1990. Phenotypic response to environmental changes. FEMS Microbiol. Ecol. 74:93102.
53. Groen, A. K.,, and H. V. Westerhoff,. 1990. Modern control theories: a consumer's test, p. 110118. In A. Cornish-Bowden, and M. L. Cardenas (ed.). Control of Metabolic Processes. NATO ASI series A: life sciences, vol. 190. Plenum Press, New York.
54. Han, K.,, and O. Levenspiel. 1988. Extended monod kinetics for substrate, product and cell inhibition. Biotechnol. Bioeng. 32:430437.
55. Harder, A.,, and J. A. Roels. 1982. Application of simple structured models in bioengineering. Adv. Biochem. Eng. 21:51107.
56. Heijnen, J. J.,, A. H. Terwisscha van Scheltinga,, and A. J. Straathof. 1992. Fundamental bottlenecks in the application of continuous bioprocesses. J. Biotechnol. 22:320.
57. Heinisch, J. 1986. Isolation and characterization of the two structural genes coding for phosphofructokinase in yeast. Mol. Gen. Genet. 202:7582.
58. Heinrich, R.,, and T. A. Rapoport. 1974. A linear steady-state treatment of enzymatic chains: general properties, control and effector strength. Eur. J. Biochem. 42:8995.
59. Hellingwerf, K. J.,, and W. N. Konings. 1985. The energy flow in bacteria: the main free energy intermediates and their regulatory role. Adv. Microb. Physiol. 26:125154.
60. Hellingwerf, K. J.,, J. S. Lolkema,, R. Otto,, O. M. Neijssel,, A. H. Stouthamer,, W. Harder,, K. van Dam,, and H. V. Westerhoff. 1982. Energetics of microbial growth: an analysis of the relationship between growth and its mechanistic basis by mosaic non-equilibrium thermodynamics. FEMS. Microbiol. Lett. 15:717.
61. Hemila, H.,, L. M. Glode,, and I. Palva. 1989. Production of diphtheria toxin CRM 228 in Bacillus subtilis. FEMS Microbiol. Lett. 53:193198.
62. Henner, D. J.,, E. Ferrari,, M. Perego,, and J. A. Hoch. 1988. Location of the targets of the hpr-97, sacU32(Hy), and sacQ36(Hy) mutations in upstream regions of the subtilisin promoter. J. Bacteriol. 170:296300.
63. Herbert, D., 1958. Some principles of continuous cultivation, p. 381396. In G. Tunevall (ed.), Recent Progress in Microbiology. Almqvist and Wiksell, Stockholm.
64. Herbert, D. 1961. The chemical composition of microorganisms as a function of their environment. Symp. Soc. Gen. Microbiol. 11:391416.
65. Herbert, D.,, R. Elsworth,, and R. C. Telling. 1956. The continuous culture of bacteria; a theoretical and experimental study. J. Gen. Microbiol. 14:601622.
66. Hlmanen, J. P.,, S. Taira,, M. Saruas,, and K. Runebery-Nyman. 1990. Expression of pertussis toxin subunit S4 as an intracytoplasmic protein in Bacillus subtilis. Vaccine 8:600604.
67. Hoch, J. A. 1991. Genetic analysis in Bacillus subtilis. Methods Enzymol. 204:305320.
68. Honjo, M.,, A. Akaoka,, A. Nakayama,, and Y. Furutani. 1986. Secretion of human growth hormone in Bacillus subtilis using prepropeptide coding region of Bacillus amyloliquefaciens neutral protease gene. J. Biotechnol. 4:6371.
69. Iijima, S.,, K. H. Lin,, and T. Kobayashi. 1991. Increased production of cloned β-galactosidase in two-stage culture of Bacillus amyloliquefaciens. J. Ferment. Bioeng. 71:6971.
70. Jeong, J. W.,, J. Snay,, and M. M. Ataai. 1990. A mathematical model for examining growth and sporulation processes of Bacillus subtilis. Biotechnol. Bioeng. 35: 160184.
71. Jöbses, I. M. L.,, G. T. C. Egberts,, A. van Baalen,, and J. A. Roels. 1985. Mathematical modelling of growth and substrate conversion of Zymomonas mobilis at 30 and 35°C. Biotechnol. Bioeng. 27:984995.
72. Jones, C. W., 1988. Membrane-associated energy transduction in Bacteria, p. 182. In C. Anthony (ed.), Bacterial Energy Transduction. Academic Press, Inc., New York.
73. Joshi, A.,, and B. O. Falsson. 1988. Escherichia coli growth dynamics: a three-pool biochemically based description. Biotechnol. Bioeng. 31:102116.
74. Kacser, H., 1988. Regulation and control of metabolic pathways, p. 123. In M. J. Bazin, and J. I. Prosser (ed.). Physiological Models in Microbiology, vol. 1. CRC Press, Inc., Boca Raton, Fla.
75. Kacser, H.,, and J. A. Burns. 1973. The control of flux. Symp. Soc. Exp. Biol. 27:65104.
76. Kacser, H.,, and J. W. Porteous. 1987. Control of metabolism: what do we have to measure? Trends Biotechnol. 12:515.
77. Kell, D. B.,, K. van Dam,, and H. V. Westerhoff,. 1989. Control analysis of microbial growth and productivity, p. 6193. In S. Baumberg,, I. Hunter,, and M. Rhodes (ed.). Microbial Products: New Approaches. 44th Symposium of the Society of General Microbiology, Cambridge University Press, Cambridge.
78. Kell, D. B.,, and H. V. Westerhoff. 1986. Metabolic control theory: its role in microbiology and biotechnology. FEMS Microbiol. Rev. 39:305320.
79. Kell, D. B.,, and H. V. Westerhoff. 1986. Towards a rational approach to the optimization of flux in microbial biotransformations. Trends Biotechnol. 20:137142.
80. Kell, D. B.,, and H. V. Westerhoff,. 1990. Control analysis of organized multienzyme systems, p. 273289. In P. A. Srere,, M. E. Jones,, and C. K. Mathews (ed.). Structural and Organizational Aspects of Metabolic Regulation. Wiley-Liss Inc., New York.
81. Khovreychev, M. P.,, A. N. Slobodkln,, Z. V. Sakharova,, and T. P. Blokhlna. 1990. Growth and development of Bacillus thuringiensis in multiple stage continuous cultivation. Mikrobiologiya 59:9981003.
82. Klelnkauf, H.,, and H. von Dohren. 1983. Non-ribosomal peptide formation on multifunctional proteins. Trends. Biochem. Sci. 8:281283.
83. Konings, W. N.,, B. Poolman,, and A. J. M. Driessen. 1992. Can the excretion of metabolites by bacteria be manipulated? FEMS Microbiol. Rev. 88:93108.
84. Kono, T.,, and T. Asai. 1969. Kinetics of fermentation processes. Biotechnol. Bioeng. 11:293321.
85. Kubltschek, H. E.,, and S. R. Pal. 1988. Variation in precursor pool size during the division cycle of Escherichia coli: further evidence for linear cell growth. J. Bacterial 170:431435.
86. Kubo, M.,, and T. Imanaka. 1989. mRNA secondary structure in an open reading frame reduces translation efficiency in Bacillus subtilis. J. Bacteriol. 171:40804082.
87. Kunkel, B. 1991. Compartmentalized gene expression during sporulation in Bacillus subtilis. Trends Genet. 7:167173.
88. Lan Wong, S.,, F. Kawamura,, and R. Doi. 1986. Use of the Bacillus subtilis signal peptide for efficient secretion of TEM β-lactamase during growth. J. Bacteriol. 168: 10051009.
89. Lecadet, M. M.,, J. Chaufaux,, J. Ribier,, and D. Lereclus. 1992. Construction of novel Bacillus thuringiensis strains with different insecticidal activities by transduction and transformation. Appl. Environ. Microbiol. 58:840849.
90. Lee, J.,, and W. F. Ramirez. 1992. Mathematic modelling of induced foreign protein production by recombinant bacteria. Biotechnol. Bioeng. 39:635646.
91. Levensplel, O. 1980. The Monod equation: a revisit and a generalization to product inhibition situations. Biotechnol. Bioeng. 22:16711687.
92. Linton, J. D. 1991. Metabolite overproduction and growth efficiency. Antonie van Leeuwenhoek Int. J. Gen. Mol. Microbiol. 60:293311.
93. Linton, J. D.,, and A. J. Rye. 1989. The relationship between the energetic efficiency in different microorganisms and the rate of metabolite overproduced. J. Ind. Microbiol. 4:8596.
94. Linton, J. D.,, and R. J. Stephenson. 1978. A preliminary study on growth yields in relation to the carbon and energy content of various organic growth substrates. FEMS Microbiol. Lett. 3:9598.
95. Losick, R.,, and P. Stragier. 1992. Crisscross regulation of cell-type-specific gene expression during development in B. subtilis. Nature (London) 355:601604.
96. Luedeking, R.,, and E. L. Piret. 1959. A kinetic study of the lactic acid fermentation. J. Biochem. Microb. Technol. Eng. 1:393412.
97. Lundstrom, K.,, I. Palva,, L. Kaarialnen,, H. Garoff,, M. Saruas,, and R. Pettersson. 1985. Secretion of Semliki-Forest virus membrane glycoprotein F-l from Bacillus subtilis. Virus Res. 2:6983.
98. Magasanik, B.,, and F. C. Neidhardt,. 1987. Regulation of carbon and nitrogen utilization, p. 13181325. In F. C. Neidhardt,, J. L. Ingraham,, K. B. Low,, M. Schaechter,, and H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology, vol 2. American Society for Microbiology, Washington, D.C.
99. Malek, I. 1958. The physiological state of microorganisms during continuous culture, p. 1128. In Continuous Cultivation of Microorganisms: a Symposium. Academia Publishing House of the Czechoslovak Academy of Science, Prague.
100. Mandelstam, J.,, K. McQuillen,, and I. Davles. 1982. Biochemistry of Bacterial Growth. Blackwell, Oxford.
101. McDuffie, N. G. 1991. Bioreactor Design Fundamentals. Butterworth-Heinemann, Stoneham, Mass.
102. Miller, J.,, S. Kovacevic,, and L. Veal. 1987. Secretion and processing of staphylococcal nuclease by Bacillus subtilis. J. Bacteriol. 169:35083514.
103. Mlnkevich, I. G.,, and V. K. Eroshln. 1973. Productivity and heat generation of fermentation under oxygen limitation. Folia Microbiol. 18:376386.
104. Monaghan, R.,, and L. Koupal,. 1989. Use of the Plackett and Burman technique in a discovery program for new natural products, p. 94116. In A. L. Demain (ed.). Novel Microbial Products for Medicine and Agriculture Society for Industrial Microbiology, Arlington, Va.
105. Monod, J. 1942. Recherches sur la croissance des cultures bactirienne. Hermann & Cie, Paris.
106. Monod, J. 1950. La technique de culture continue. Theorie et applications. Ann. Inst. Pasteur 79:390410.
107. Moser, A., 1985. Imperfectly mixed bioreactor systems, p. 7798. In C. L. Cooney, and A. E. Humphrey (ed.), Comprehensive Biotechnology; the Principles, Applications and Regulations of Biotechnology in Industry, Agriculture and Medicine, vol. 2. Pergamon Press, Oxford.
108. Mulder, M. M.,, H. M. L. van der Gulden,, P. W. Postma,, and K. van Dam. 1988. Effect of macromolecular composition of microorganisms on the thermodynamic description of their growth. Biochim. Biophys. Acta 936: 406412.
109. Nagarajan, V. 1990. System for secretion of heterologous proteins in Bacillus subtilis. Methods Enzymol. 185:214223.
110. Nagarajan, V.,, and M. Chen. 1991. The role of precursor conformation on protein secretion in Bacillus subtilis. Abstract 6th Int. Conf. Bacilli, Stanford, Calif.
111. Nakazawa, K.,, H. Sasamoto,, Y. Shirakl,, S. Harada,, K. Yanagi, and K. Yamane. 1991. Extracellular production of mouse interferon beta by the Bacillus subtilis alpha-amylase secretion vectors: antiviral activity and deduced NH2-terminal amino acid sequences of the secreted proteins. Intervirology 32:216227.
112. Neijssel, O. M.,, and D. W. Tempest. 1976. The role of energy-spilling reactions in the growth of Klebsiella aerogenes NCTC418 in aerobic chemostat culture. Arch. Microbiol. 110:305311.
113. Neijssel, O. M.,, and D. W. Tempest. 1976. Bioenergetic aspects of aerobic growth of Klebsiella aerogenes NCTC 418 in carbon-limited and carbon-sufficient chemostat cultures. Arch. Microbiol. 107:215221.
114. Neijssel, O. M.,, and D. W. Tempest. 1979. The physiology of metabolite overproduction. Symp. Soc. Gen. Microbiol. 29:5382.
115. Nicholson, W. L.,, and G. H. Chambliss. 1985. Isolation and characterization of a cis-acting mutation conferring catabolite repression resistance to alpha-amylase synthesis in Bacillus subtilis. J. Bacteriol. 161:875881.
116. Nimmo, H. G.,, and P. T. W. Cohen. 1987. Applications of recombinant DNA technology to studies of metabolic regulation. Biochem. J. 247:113.
117. Novick, A.,, and L. Szilard. 1950. Experiments with the chemostat on spontaneous mutations of bacteria. Proc. Natl. Acad. Sci. USA 36:708719.
118. Novlkov, S.,, I. Borukhov,, and A. Strongin. 1990. Bacillus amyloliquefaciens α-amylase signal sequence fused in frame with human proinsulin is properly processed by Bacillus subtilis cells. Biochem. Biophys. Res. Commun. 169:297301.
119. Ochi, K.,, J. C. Kandala,, and E. Freese. 1981. Initiation of Bacillus subtilis sporulation by the stringent response to amino acid deprivation. J. Biol. Chem. 256:68666875.
120. Ochi, K.,, J. Kandala,, and E. Freese. 1982. Evidence that Bacillus subtilis sporulation induced by the stringent response is caused by the decrease in GTP or GDP. J. Bacteriol. 151:10621065.
121. O'Connor, R.,, W. H. Elliott,, and B. K. May. 1978. Modulation of an apparent mRNA pool for extracellular protease in Bacillus amyloliquefaciens. J. Bacteriol. 136:2434.
122. Overbeeke, N.,, H. Geertruida,, M. Termorshuizen,, M. Giuseppin,, D. Underwood,, and C. Verrips. 1989. Secretion of the α-galactosidase from Cyamopsis tetragonoloba (guar) by Bacillus subtilis. Appl. Environ. Microbiol. 56:193198.
123. Owens, J. D.,, and J. D. Legan. 1987. Determination of the Monod substrate saturation constant for microbial growth. FEMS Microbiol. Rev. 46:419432.
124. Pagni, M.,, T. Beffa,, C. Isch,, and M. Aragno. 1992. Linear growth and poly(β-hydroxybutyrate) synthesis in response to pulse-wise addition of the growth-limiting substrate to steady-state heterotrophic continuous cultures of Aquaspirillum autotrophicum. J. Gen. Microbiol. 138:429436.
125. Panikov, N.,, and S. J. Pirt. 1978. The effects of cooperativity and growth yield variation on the kinetics of nitrogen or phosphate-limited growth of Chlorella in a chemostat culture. J. Gen. Microbiol. 108:295303.
126. Papoutsakls, E. T.,, and C. L. Meyer. 1985. Equations and calculations of product yields and preferred pathways for butanediol and mixed-acid fermentations. Biotechnol. Bioeng. 27:5066.
127. Payne, M. S.,, and E. N. Jackson. 1991. Use of alkaline phosphatase fusions to study protein secretion in Bacillus subtilis. J. Bacteriol. 173:22782282.
128. Payne, W. J. 1970. Energy yields and growth of heterotrophs. Annu. Rev. Microbiol. 24:1752.
129. Perego, M.,, C. F. Higgins,, S. R. Pearce,, M. P. Gallagher,, and J. A. Hoch. 1991. The oligopeptide transport system of Bacillus subtilis plays a role in the initiation of sporulation. Mol. Microbiol. 5:173185.
129a.. Perklns, J. B.,, J. G. Pero,, and A. Sloma. January 1991. Riboflavin overproducing strains of bacteria. European patent application 90111916.4.
130. Pierce, J. A.,, C. R. Robertson,, and T. J. Leighton. Physiological and genetic strategies for enhanced subtilisin production by Bacillus subtilis. Biotechnol. Prog., in press.
131. Pirt, S. J. 1965. The maintenance energy of bacteria in growing cultures. Proc. R. Soc. Land. Sect. B 163:224231.
132. Pirt, S. J. 1975. Principles of Microbe and Cell Cultivation. Blackwell, Oxford.
133. Pirt, S. J. 1982. Maintenance energy: a general model for energy-limited and energy-sufficient growth. Arch. Microbiol. 133:300302.
134. Pirt, S. J. 1987. The energetics of microbes at slow growth rates: maintenance energies and dormant organisms. J. Ferment. Technol. 65:173177.
135. Powell, E. O. 1967. The growth rate of microorganisms as a function of substrate concentration, p. 3456. In Microbial Physiology and Continuous Culture. Proceedings of the 3rd International Symposium. Her Majesty's Stationary Office, London.
136. Powell, E., 0.1969. Transient changes in the growth rate of microorganisms, p. 275284. In I. Malek,, K. Beran,, Z. Fencl,, V. Munk,, J. Ricica,, and H. Smrckova (ed.), Continuous Cultivation of Microorganisms. Proceedings of the 4th International Symposium. Acadamia, Prague.
137. Priest, F. 1977. Extracellular enzyme synthesis in the genus Bacillus. Bacteriol. Rev. 41:711753.
138. Priest, F. G., 1989. Products from bacilli, p. 293315. In C. F. Harwood (ed.), Handbooks of Biotechnology, vol. 2. Bacillus. Plenum Press, New York.
139. Priest, F. G. 1992. Biological control of mosquitos and other biting flies by Bacillus sphaericus and Bacillus thuringiensis—a review. J. Appl. Bacteriol. 72:357369.
140. Priest, F. G.,, and R. J. Sharp,. 1989. Fermentation of bacilli, p. 73132. In J. O. Neway (ed.). Fermentation Process of Development of Industrial Organisms. Marcel Dekker, Inc., New York.
141. Ramkrishna, D.,, D. S. Kompala,, and G. T. Tsao,. 1984. Cybernetic modelling of microbial populations: growth on mixed substrates, p. 241261. In L. K. Doraiswamy, and R. A. Mashelkar (ed.), Frontiers in Chemical Reaction Engineering. Wiley Eastern, New Delhi, India.
142. Reda, K. D.,, and D. R. Omstead,. 1990. Automatic fermentor sampling and stream analysis, p. 73107. In D. R. Omstead (ed.), Computer Control of Fermentation Processes. CRC Press, Boca Raton, Fla.
143. Resnek, O.,, L. Rutberg,, and A. von Gabain. 1990. Changes in the stability of specific mRNA species in response to growth stage in Bacillus subtilis. Proc. Natl. Acad. Sci. USA 87:83558359.
144. Roels, J. A. 1980. Application of macroscopic principles to microbial metabolism. Biotechnol. Bioeng. 22:24572514.
145. Roels, J. A. 1981. The application of macroscopic principles to microbial metabolism. Ann. N.Y. Acad. Sci. 369:113134.
146. Ross, R.,, J. D'Elia,, R. Mooney,, and W. Chesbro. 1990. Nutrient limitation of two saccharolytic Clostridia: secretion, sporulation, and solventogenesis. FEMS Microbiol. Ecol. 74:153164.
147. Rutgers, M. 1990. Control and thermodynamics of microbial growth. Ph.D. thesis. University of Amsterdam, Amsterdam, The Netherlands.
148. Rutgers, M.,, P. A. Balk,, and K. van Dam. 1989. Thermodynamic efficiency of bacterial growth calculated from growth yield of Pseudomonas oxalaticus OX1 in the chemostat. Biochim. Biophys. Acta 973:302307.
149. Rutgers, M.,, P. A. Balk,, and K. van Dam. 1990. Quantification of multiple substrate controlled growth— simultaneous ammonium and glucose limitation in chemostat cultures of Klebsiella pneumoniae. Arch. Microbiol. 153:478484.
150. Rutgers, M.,, K. van Dam,, and H. V. Westerhoff. 1991. Control and thermodynamics of microbial growth: rational tools for bioengineering. Crit. Rev. Biotechnol. 11:367395.
151. Sari, P.,, S. Taira,, U. Alraksinen,, A. Palva,, M. Sarvas,, and K. Runeberg-Nyman. 1990. Production and secretion of pertussis toxin subunits in Bacillus subtilis. FEMS Microbiol. Lett. 56:143148.
152. Saunders, C.,, B. Schmidt,, R. Mallonee,, and M. Guyer. 1987. Secretion of human serum albumin from Bacillus subtilis. J. Bacteriol. 169:29172925.
153. Saunders, C. W.,, J. A. Pedronl,, and P. M. Monahan. 1991. Optimization of the signal-sequence cleavage site for secretion from Bacillus subtilis of a 34-amino acid fragment of human parathyroid hormone. Gene 102: 277282.
154. Schein, C. H.,, K. Kashiwagl,, A. Fujljawa,, and C. Welssmann. 1986. Secretion of mature interferon alpha-2 and accumulation of uncleaved precursor by Bacillus subtilis transformed with a hybrid alpha amylase signal sequence interferon alpha-2 gene. Bio/Technology 4:719725.
155. Scheller, F.,, and F. Schubert. 1992. Biosensors. Elsevier Science Publishing, Amsterdam.
156. Schugerl, K.,, and W. Sittig,. 1987. Bioreactors, p. 179224. In P. Prave,, U. Faust,, W. Sittig,, and D. A. Sukatsch (ed.), Fundamentals of Biotechnology. VCH Verlagsgesellschaft, Weinheim, Germany.
157. Setlow, P. 1973. Inability to detect cAMP in vegetative or sporulating cells or dormant spores of Bacillus megaterium. Biochem. Biophys. Res. Commun. 52:365372.
158. Shu, J.,, and M. L. Shuler. 1989. A mathematical model for the growth of a single cell of E. coli on a glucose/ glutamine/ammonium medium. Biotechnol. Bioeng. 33: 11171126.
159. Shuler, M. L., 1985. Dynamic modelling of fermentation systems, p. 119131. In C. L. Cooney, and A. E. Humphrey (ed.), Comprehensive Biotechnology: the Principles, Applications and Regulations of Biotechnology in Industry, Agriculture and Medicine, vol. 1. Pergamon Press, Oxford.
160. Shuler, M. L.,, and M. M. Domach,. 1983. Mathematical models of the growth of individual cells. Tools for testing biochemical mechanisms, p. 93133. In H. W. Blanch,, E. T. Papoutsakis,, and G. Stephanopoulos (ed.), Foundations of Biochemical Engineering, kinetics and Thermodynamics in Biological Systems. ACS symposium series 207. American Chemical Society, Washington, D.C.
161. Shuyler, M.,, and W. Forman. 1984. Alvedar macrophage plasminogen activator. Exp. Lung Res. 6:159169.
162. Siegele, D. A.,, and R. Kolter. 1992. Life after log. J. Bacteriol. 174:345348.
163. Slater, J. H., 1985. Stoichiometry of microbial growth, p. 189213. In C. L. Cooney, and A. E. Humphrey (ed.), Comprehensive Biotechnology: the Principles, Applications and Regulations of Biotechnology in Industry, Agriculture and Medicine, vol. 1. Pergamon Press, Oxford.
164. Sonenshein, A. L., 1989. Metabolic regulation of sporulation and other stationary-phase phenomena, p. 109130. In I. Smith,, R. A. Slepecky,, and P. Setlow (ed.), Regulation of Procaryotic Development. American Society for Microbiology, Washington, D.C.
165. Stackebrant, F.,, and C. F. Woese. 1981. The evolution of prokaryotes. Symp. Soc. Gen. Microbiol. 32:132.
166. Starzak, M.,, and R. K. Bajpai. 1991. A structured model for vegetative growth and sporulation in Bacillus thuringiensis. Appl. Biochem. Biotechnol. 28/29:699718.
167. Stephanopoulos, G. 1986. Application of macroscopic balances and bioenergetics of growth to the on-line identification of biological reactors. Ann. N.Y. Acad. Sci. 469:332349.
168. Stouthamer, A. H., 1979. The search for correlation between theoretical and experimental growth yields, p. 147. In J. R. Quayle (ed.), International Review of Biochemistry, vol. 21. Microbial Biochemistry. University Park Press, Baltimore.
169. Stouthamer, A. H.,, B. A. Bulthuis,, and H. W. van Verseveld,. 1990. Energetics of growth at low growth rates and its relevance for the maintenance concept, p. 85102. In R. K. Poole,, M. J. Bazin,, and W. Keevil (ed.), Microbial Growth Dynamics. Society for General Microbiology special publication 28. IRL Press, Oxford.
170. Stouthamer, A. H.,, and H. W. van Verseveld,. 1985. Stoichiometry of microbial growth, p. 215238. In C. L. Cooney, and A. E. Humphrey (ed.), Comprehensive Biotechnology: the Principles, Applications and Regulations of Biotechnology in Industry, Agriculture and Medicine, vol. 1. Pergamon Press, Oxford.
171. Stouthamer, A. H.,, and H. W. van Verseveld. 1987. Microbial energetics should be considered in manipulating metabolism for biotechnological purposes. Trends Biotechnol. 5:149155.
172. Stucki, J. W. 1980. The optimal efficiency and the economic degrees of coupling of oxidative phosphorylation. Eur. J. Biochem. 109:269283.
173. Suh, J. W.,, S. A. Boylan,, S. M. Thomas,, K. M. Dolan,, D. B. Oliver,, and C. W. Price. 1990. Isolation of a secY homologue from Bacillus subtilis: evidence for a common protein export pathway in eubacteria. Mol. Microbiol. 4:305314.
174. Taira, S.,, E. Julonen,, J. Paton,, M. Saruas,, and K. Runeberg-Nyman. 1990. Production of pneumolysin, a pneumococcal toxin, in Bacillus subtilis. Gene 77:211218
175. Tempest, D. W.,, D. Herbert,, and P. J. Phlpps,. 1967. Studies on the growth of Aerobacter aerogenes at low dilution rates in a chemostat, p. 240254. In E. O. Powell,, C. G. T. Evans,, R. E. Strange,, and D. W. Tempest (ed.), Microbial Physiology and Continuous Culture. Her Majesty's Stationary Office, London.
176. Tempest, D. W.,, and O. M. Nijssel,. 1980. Comparative aspects of microbial growth yields with special reference to C, utilizers, p. 325334. In H. Dalton (ed.), Microbial Growth on C, Compounds. Heyden, London.
177. Thatipamala, R.,, S. Rohani,, and G. A. Hill. 1992. Effects of high product and substrate inhibitions on the kinetics and biomass and product yields during ethanol batch fermentation. Biotechnol. Bioeng. 40:289297.
178. Tsai, S. P.,, and Y. H. Lee. 1990. A model for energy-sufficient culture growth. Biotechnol. Bioeng. 35:138145.
179. Turner, B. G.,, and D. Ramkrlshna. 1988. Revised enzyme synthesis rate expression in cybernetic models of bacterial growth. Biotechnol. Bioeng. 31:4143.
180. Turner, B. G.,, D. Ramkrlshna,, and N. B. Jansen. 1989. Cybernetic modelling of bacterial cultures at low growth rates: single substrate systems. Biotechnol. Bioeng. 34:252261.
181. Valle, F.,, and E. Ferrari,. 1989. Subtilisin: a redundantly temporally regulated gene?, p. 131146. In I. Smith,, R. A. Slepecky,, and P. Setlow (ed.), Regulation of Procaryotic Development. American Society for Microbiology, Washington, D.C.
182. van Dam, K.,, M. M. Mulder,, J. Teixera de Mattos,, and H. V. Westerhoff,. 1988. A thermodynamic view of bacterial growth, p. 2548. In M. J. Bazin, and J. I. Prosser (ed.), Physiological Models in Microbiology, vol. 1. CRC Press, Boca Raton, Fla.
183. van der Laan, J. C.,, G. Gerriste,, L. J. S. M., Mulliners,, R. A. C. Van Der Hoek,, and W. J. Quax. 1991. Cloning, characterization, and multiple chromosomal integration of a Bacillus alkaline protease gene. J. Bacteriol. 57:901909.
184. van Dijl, J. M.,, A. de Jong,, J. Vehmaanpera,, G. Venema,, and S. Bron. 1991. Bacillus subtilis signal peptidase I. Abstr. 6th Int. Conf. Bacilli, Stanford, Calif.
185. van Verseveld, H. W.,, M. Arbige,, and W. R. Chesbro. 1984. Continuous culture of bacteria with biomass retention. Trends Biotechnol. 2:812.
186. van Verseveld, H. W.,, J. P. Boon,, and A. H. Stouthamer. 1979. Growth yields and efficiency of oxidative phosphorylation of Paracoccus denitrificans during two (carbon) substrate-limited growth. Arch. Microbiol. 121: 213223.
187. van Verseveld, H. W.,, W. R. Chesbro,, M. Braster,, and A. H. Stouthamer. 1984. Eubacteria have 3 growth modes keyed to nutrient flow. Consequences for the concept of maintenance and maximal growth yield. Arch. Microbiol. 137:176184.
188. van Verseveld, H. W.,, J. A. de Hollander,, J. Frankena,, M. Braster,, F. J. Leeuwerik,, and A. H. Stouthamer. 1986. Modelling of microbial substrate conversion, growth and product formation in a recycling fermentor. Antonie van Leeuwenhoek J. Microbiol. 52:325342.
189. van Verseveld, H. W.,, and A. H. Stouthamer. 1978. Growth yields and the efficiency of oxidative phosphorylation during autotrophic growth of Paracoccus denitrificans on methanol and formate. Arch. Microbiol. 118:2126.
190. Vasantha, N.,, and D. Filpula. 1989. Expression of bovine pancreatic ribonuclease A coded by a synthetic gene in Bacillus subtilis. Gene 76:5360.
191. Vasantha, N.,, and L. Thompson. 1986. Fusion of Pro region of subtilisin to staphylococcal protein A and its secretion of Bacillus subtilis. Gene 49:2328.
192. Volkering, F.,, A. M. Breure,, A. Sterkenburg,, and J. G. van Andel. 1992. Microbial degradation of polycyclic aromatic hydrocarbons: effect of substrate availability on bacterial growth kinetics. Appl. Microbiol. Biotechnol. 36:548552.
193. von Stockar, U.,, and L. C. M. Auberson. 1992. Chemostat cultures of yeasts, continuous culture fundamentals and simple unstructured models. J. Biotechnol. 22:6988.
194. Wang, L. F.,, S. L. Wong,, S. G. Lee, N. K. Kalyan, P. Hung, S. Hilliker, and R. H. Dot. 1988. Expression and secretion of human atrial natriuretic α-factor in Bacillus subtilis using the subtilisin signal peptide. Gene 69:3947.
195. Wang, N. S.,, and G. Stephanopoulos. 1983. Application of macroscopic balances to the identification of gross measurement errors. Biotechnol. Bioeng. 25:21772208.
196. Wanner, U.,, and T. Egli. 1990. Dynamics of microbial growth and cell composition in batch culture. FEMS Microbiol. Rev. 75:1944.
197. Weickert, M. J.,, L. Larson,, W. L. Nicholson,, and G. H. Chambliss,. 1990. Negative control of amylase synthesis: mutations which eliminate catabolite repression or temporal turn-off, p. 237244. In M. M. Zukowski,, A. T. Ganesan,, and J. A. Hoch (ed.), Genetics and Biotechnology of the Bacilli. American Society for Microbiology, Washington, D.C.
198. Wells, J. A.,, and D. A. Estell. 1988. Subtilisin—an enzyme designed to be engineered. Trends Biol. Sci. 13:291297.
199. Westerhoff, H. V.,, K. J. Hellingwerf,, and K. van Dam. 1983. Thermodynamic efficiency of microbial growth is low but optimal for maximal growth rate. Proc. Natl. Acad. Sci. USA 80:305309.
200. Westerhoff, H. W.,, and D. B. Kell. 1987. Matrix method for determining steps most rate-limiting to metabolic fluxes in biotechnological processes. Biotechnol. Bioeng. 30:101107.
201. Westerhoff, H. v.,, J. S. Lolkema,, R. Otto,, and K. J. Hellingwerf. 1982. Nonequilibrium thermodynamics of bacterial growth. The phenomenological and the mosaic approach. Biochim. Biophys. Acta 683:181220.
202. Wu, X. C.,, W. Lee,, L. Tran,, and S. L. Wong. 1991. Engineering a Bacillus subtilis expression-secretion system with a strain deficient in six extracellular proteases. J. Bacteriol. 173:49524958.
203. Yamagata, H.,, K. Nakahama,, Y. Suzuki,, A. Kakinuma,, N. Tsukayoshi,, and S. Udaka. 1989. Use of Bacillus— brews for efficient synthesis and secretion of human epidermal growth factor. Proc. Natl. Acad. Sci. USA 86:35893593.
204. Yamane, T.,, and S. Shimizu. 1984. Fed-batch techniques in microbial processes. Adv. Biochem. Eng. Biotechnol. 30:147194.
205. Young, T. B.,, and H. R. Bungay. 1973. Dynamic analysis of a microbial process: a systems engineering approach. Biotechnol. Bioeng. 15:377393.
206. Zukowski, M.,, and L. Miller. 1986. Hyperproduction of an intracellular heterologous protein in a sac U mutant of Bacillus subtilis. Gene 46:247255.

Tables

Generic image for table
Table 1

Examples of enzymes in commerce

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60
Generic image for table
Table 2

Examples of recombinant proteins synthesized and secreted in spp.

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60
Generic image for table
Table 3

Some examples of adapted Monod equations

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60
Generic image for table
Table 4

Comparison of aerobic growth and production of in RF and CF

Citation: Arbige M, Bulthuis B, Schultz J, Crabb D. 1993. Fermentation of Bacillus, p 871-895. In Sonenshein A, Hoch J, Losick R (ed), and Other Gram-Positive Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555818388.ch60

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error