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Metabolite production and growth efficiency

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Abstract

The capacity to sustain the large fluxes of carbon and energy required for rapid metabolite production appears to be inversely related to the growth efficiency of micro-organisms. From an overall energetic point of view three main classes of metabolite may be distinguished. These are not discrete categories, as the energetics of biosynthesis will depend on the precise biochemical pathways used and the nature of the starting feed stock(s). (1) for metabolites like exopolysaccharides both the oxidation state and the specific rate of production appear to be inversely related to the growth efficiency of the producing organism. Maximum rates of production are favored when carbon and energy flux are integrated, and alteration of this balance may negatively effect production rates. (2) The production of metabolites like organic acids and some secondary metabolites results in the net production of reducing equivalents and/or ATP. It is thought that the capacity of the organism to dissipate this product associated energy limits its capacity for rapid production. (3) For metabolites like biosurfactants and certain secondary metabolites that are composed of moieties of significantly different oxidation states production from a single carbon source is unfavorable and considerable improvements in specific production rate and final broth concentration may be achieved if mixed carbon sources are used. By careful selection of production organism and starting feedstock(s) it may be possible to tailor the production, such that the adverse physiological consequences of metabolite overproduction on the production organism are minimized.

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References

  • Anderson A, Hacking AJ & Dawes E (1987) Alternative pathway for the biosynthesis of alginate from fructose and glucose in Pseudomonas mendocina and Azotobacter vinelandii. J. Gen. Microbiol. 133: 1045–1052

    Google Scholar 

  • Andrew SPS (1983) Old and new feedstocks-chemistry and commerce. Inst Chemical Engineers Symposium. Series no. (79 pp 400–408)

  • Betlac MR, Campage MA Doherty DH Hasster RA Henderson NM Vanderslice RW Marelli JD & Ward MB (1987) Genetically engineered polymers: manipulation of xanthan biosynthesis. In: Yalpani M (Ed) Industrial Polysaccharides. Programme in Biotechnology, Vol 3 (pp 35–50) Elsevier, Amsterdam

    Google Scholar 

  • Cooper DG & Paddock DA (1984) Production of a biosurfactant from Torulopsis bombicola. Appl. Environ. Microbiol. 47: 173–176

    Google Scholar 

  • Cornish A, Linton JD & Jones CW (1987) The effect of growth conditions on the respiratory system of a succinoglucan-producing strain of Agrobacterium radiobacter. J. Gen. Microbiol. 133: 1971–2978

    Google Scholar 

  • Cornish A, Greenwood JA, & Jones CW (1988a) Binding protein dependent transport glucose transport by Agrobacterium radiobacter grown in glucose limited continuous culture. J. Gen. Microbiol. 134: 3099–3110

    Google Scholar 

  • Cornish A (1988b) The relationship between glucose transport and the production of succinoglucan exopolysaccharide by Agrobacterium radiobacter. J. Gen. Microbiol. 134: 3111–3122

    Google Scholar 

  • Doherty D, Leigh JA Glazebrook J & Walker GC (1988) Rhizobium meliloti acid calcafluor-binding exopolysaccharide. J. Bacteriol. 170: 4249–4256

    Google Scholar 

  • Dunnill P (1983) The future of Biotechnology. In: Biochem. Soc. Symp. No. 48, Biotechnol. 9–23

  • Farrand SG, Jones CW Linton JD & Stephenson RJ (1983) The effect of temperature and pH on the growth efficiency of the thermoacidophilic bacterium Bacillus acidocaldarius in continuous culture. Arch. Microbiol. 135: 276–283

    Google Scholar 

  • Glazebrook J & Walker GC (1989) A novel exopolysaccharide can function in place of the calcalfuor-binding exopolysaccharide in nodulation of Alfalfa by Rhixobium meliloti. Cell: 661–672

  • Grinberg AJ, Kosenko LV & Malashenko R Yu (1984) Formation of exopolysaccharide by methylotrophic micro-organisms. Mikrobiologischeskii Zhurnal 46: 22–26

    Google Scholar 

  • Hersbach GJM, Van Der Beek CP & Van Dijk PWM (1984) The penicillins: Properties, biosynthesis and fermentation. In: Vandamme EJ (Ed) Biotechnology of Industrial Antiobiotics. Marcel Dekker, New York

    Google Scholar 

  • Huetmg S & Tempest DW (1977) Influence of acetate on the growth of Candida utilis in continuous culture. Arch. Microbiol. 115: 73–78

    Google Scholar 

  • Hoischen C & Kramer SG (1990) Evidence for efflux carrier system involved in the secretion of glutamate by Corynebacterium glutamicum. Arch. Microbiol. 151: 342–347

    Google Scholar 

  • Jarman TR & Pace GW (1984) Energy requirements for microbial exopolysaccharide synthesis. Arch. Microbiol. 137: 231–235

    Google Scholar 

  • Jones CW (1988) Aerobic respiratory systems in bacteria. In: G.Durand, L.Bobichon & JFlorent (Eds) 8th Int. Biotechnol. Symp. Vol. 1 (pp 43–55). Soc. Franc. Microbiol. Paris

    Google Scholar 

  • Kacser H & Burns JA (1973) The control of flux. In: DD Davies (Ed) Rate Control of Biological Processes. Symp. Soc. Gen. Micribiol. 27: 65–104. Cambridge

  • Kell DB (1989) Control analysis of microbial growth and productivity. In: Baumberg S, Hunter I & Rhodes M (Eds) Society for General Microbiology Symposium 44: 61–93

  • King PP (1982) Biotechnology: an industrial view. J. Chem. Tech. Biotechnol. 32: 2–8

    Google Scholar 

  • Kiyoshi K (1981) Biosynthesis of peptide antibiotics. In: Corcovan JW (Ed) Antibiotics, Vol. iv. Springer-Verlag

  • Kula MR, Aharonowitz IY, Bulock JD, Chakrabarty AM, Hopwood DA, M athiasson B, Morris JG, Neijssel OM & Sahm H (1987) Microbiology and industrial products. Group report in biotechnology: potentials and limitations (Dahlem Konferenze 1986), University Press

  • Kristiansen B & Charley R (1981) Continuous process for the production of citric acid. In: MMoo-Young (Ed) Advances in Biotechnology 1. Proceed. 16th Int. Ferment Symp Pergamon Press, Toronto

    Google Scholar 

  • Linton JD (1990) The relationship between metabolite production and growth efficiency of the producing organism. FEMS Microbiology Reviews 75: 1–18

    Google Scholar 

  • Linton JD, Austin RN & Haugh DE (1984) The kinetics and physiology of stipitatic acid and gluconate production by carbon sufficient cultures of Penicillium stipitatum growing in continuous culture. Biotechnol. Bioeng. XXVI: 1455–1464

    Google Scholar 

  • Linton JD, Griffiths J & Gregory M (1981) The effect of mixtures of glucose and formate on the yield and respiration of a chemostat culture of Beneckea natriegens. Arch. Microbiol. 129: 119–122

    Google Scholar 

  • Linton JD, Evans M Jones DS & Gouldney DN (1987a) Exocellular succinoglucan production be Agrobacterium radiobacter NCIB 11883. J. Gen. Microbiol. 133: 2961–2969

    Google Scholar 

  • Linton JD, Jones DS & Woodard S (1987b) Factors that control the rate of exopolysaccharide production by Agrogacterium radiobacter NCIB 11883 J. Gen. Microbiol. 133: 2979–2987

    Google Scholar 

  • Linton JD, Gouldney D & Woodard S (1988) Efficiency and stability of exo-polysaccharide production from different carbon sources by Erwinia herhicola. J. Gen. Microbiol. 134: 1913–1921

    Google Scholar 

  • Linton JD & Musgrove SG (1983) Product formation by a nitrogen limited culture of Beneckea natriegens in a chemostat in the presence of excess glucose. Env. J. Appl. Microbiol. Biotechnol. 18: 24–28

    Google Scholar 

  • Linton JD, Watts PD, Austin RM, Haugh DE & Niekus HGD (1986) The energetics and kinetics of extracellular polysaccharide production from methanol by organisms possessing different pathways of C-1 fixation. J. Gen. Microbiol. 132: 779–788

    Google Scholar 

  • Linton JD & Rye AR (1989) The relationship between the energetic efficiency in different microorganisms and the rate and type of metabolite over- produced. J. Indust. Microbiol. 4: 85–96

    Google Scholar 

  • Mason HRS & Righelato RC (1976) Energetics of fungal growth: Effects of growth-limiting substrate on respiration of Penicillium chrysogenum. J Appl Chem. Biotechnol. 26: 145–152

    Google Scholar 

  • Miall LM (1972) Stimulatory effect of organic acids in citric acid fermentation. UK Patent Spec. 1293786

  • Nakayama K (1976) The production of amino-acids. Proc Biochem 3: 4–9

    Google Scholar 

  • (1986) Breeding of amino-acid mutants. In: Aida K, Chidala I, Nakayama H (Eds) Biotechnology of amino acid production. Progress in Industrial Microbiology (24: 3–33 ). Elsevier, Amsterdam

  • Neijssel OM (1977) The effect of 2, 4-dinitrophenol on the growth of Klebsiella aerogenes NCTC 418 in aerobic chemostat culture. FEMS Letts. 1: 47–50

    Google Scholar 

  • Pospisil S, Sedmera P Matej J & Nohynek M (1988) Polyether Antibiotics: Monensin. Bioactive metabolites from microorganisms. In: Bushell ME & Grafe U (Eds) Progress in Microbiology 27. Elsevier, Amsterdam

    Google Scholar 

  • Righelato RC, Trinci APJ & Pirt SJ (1968) The influence of maintenance energy and growth rate on the metabolic activity, morphology and conidiation of Penicillium chrysogenum J. Gen. Microbiol. 50: 399–412

    Google Scholar 

  • Rye AJ, Drozd JW Jones CW & Linton JD (1988) Growth efficiency of Xanthomonas campestris in continuous culture. J. Gen. Microbiol. 134: 1055–1061

    Google Scholar 

  • Stark WM Knox NG & Westhead JE (1967) Monensin, a new biologically active compound II. Fermentation studies, Antimicrobial Agents & Chemoth. 353–358

  • Stouthamer AH (1979) The search for correlation between theoretical and experimental growth yields. In: Quayle JR (Ed) International Reviews of Biochemistry. Microbial Biochemistry, Vol 21 (pp 1–47). University Parks Press, Baltimore, MD

    Google Scholar 

  • Stouthamer AH & Bettenhaussen CW (1973) Determination of efficiency of oxidative phosphorylation in continuous cultures of Aerobacter aerogenes Arch. Microbiol. 102: 187–195.

    Google Scholar 

  • Stouthamer AH & van Verseveld HW (1985) In: Moo-Young M (Ed) Compehensive Biotechnology, Vol 1 (pp 215–238). Pergamon Press, Oxford

    Google Scholar 

  • Stouthamer AH (1987) Microbial energetics should be considered in manipulating metabolism for biotechnological purposes. Tr. Biotechnol. 5: 149–155

    Google Scholar 

  • Tanaka K, Iwasaki T & Kinoshita S (1960) Studies on l-glutamic acid fermentation. Part 5. Biotin and l-glutamic acid accumulation by bacteria. J. Agri. Chem. Soc. (Japan) 34: 593–600

    Google Scholar 

  • Tanaka K Machida-Shi K & Yamaguchi K (1969) Process for producing l-glutamic acid and alpha-ketoglutaric acid US Patent Office 3, 450, 599

  • Tong GE & Cannell PR (1983) The economics of organic chemicals from biomass. In: Wise DL (Ed) Organic chemicals from Biomass (pp 407–451). The Benjamin/Cummings Publishing Company Inc., London

    Google Scholar 

  • Weenk G Olijve W & Harder W (1984) Ketogluconate formation by Gluconobacter species. Appl. Microbiol. Biotechnol. 20: 400–405

    Google Scholar 

Download references

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Linton, J.D. Metabolite production and growth efficiency. Antonie van Leeuwenhoek 60, 293–311 (1991). https://doi.org/10.1007/BF00430371

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