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Effects of medium sterilization on the production of zaragozic acids by the fungusLeptodontidium elatius

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Journal of Industrial Microbiology

Abstract

The production of zaragozic acids by fermentation of the fungusLeptodontidium elatius was examined at the 800-L fermentor scale under two different production medium batch sterilization conditions. Low production-medium heat input (R0=33.4 min) resulted in a 4′-desacetoxy zaragozic acid C:4′-O-desacetyl zaragozic acid C:zaragozic acid C ratio of 0.53:0.60:1.0. At a higher heat input (R0=50.5 min), the ratio shifted to 1.0:0.66:1.0 with a corresponding 26% increase in total zaragozic acid production. This higher total zaragozic acid titer resulted from an increase in the amount of 4′-desacetoxy zaragozic acid C produced while the levels of the other two analogues remained unchanged. Batch sterilization conditions also resulted in differences in growth, carbon substrate consumption, and oxygen uptake rates. The structures of the zaragozic acids produced suggest a precursor/end product relationship. A biosynthetic model describing the synthesis of the three zaragozic acids listed above is postulated and used to explain the effects of production-medium heat input during sterilization.

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References

  1. Anderson TM, EA Bodie, N Goodman and RD Schwartz. 1986. Inhibitory effect of autoclaving whey-based medium on propionic acid production byPropionibacterium shermanii. Appl Environ Microbiol 51: 427–428.

    Google Scholar 

  2. Bergstrom JD, C Dufresne, GF Bills, M Nallin-Omstead and K Byrne. 1995. Discovery, biosynthesis and mechanism of action of the zaragozic acids: potent inhibitors of squalene synthase. Annu Rev Microbiol (in press).

  3. Bergstrom JD, MM Kurtz, DJ Rew, AM Amend, JD Karkas, RG Bostedor, VS Bansal, C Dufresne, FL VanMiddlesworth, OD Hensens, JM Liesch, DL Zink, KE Wilson, J Onishi, JA, Milligan, G Bills, L Kaplan, M Nallin Omstead, RG Jenkins, L Huang, MS Meinz L Quinn, RW Burg, YL Kong, S Mochales, M Mojena, I Martin, F Pelaez, MT Diez and AW Alberts. 1993. Zaragozic acids: a family of fungal metabolites that are picomolar competitive inhibitors of squalene synthase. Proc Natl Acad Sci USA 90: 80–84.

    PubMed  Google Scholar 

  4. Bills GD, F Pelaez, JD Polishook, MT Diez-Matas, GH Harris, WH Clapp, C Dufresne, KM Byrne, M Nallin-Omstead, RG Jenkins, M Mojena, L Huang, and JD Bergstrom. 1994. Distribution of zaragozic acids (squalestatins) among filamentous ascomycetes. Mycol Res 98: 733–739.

    Google Scholar 

  5. Boeck LD, RW Wetzel, SC Burt, FM Huber, GL Fowler and JS Alford. 1988. Sterilization of bioreactor media on the basis of computer calculated thermal input designated as F0. J Ind Microbiol 3: 305–310.

    Google Scholar 

  6. Boeck LD, JS Alford, RL Pieper and FL Huber. 1989. Interaction of media components during bioreactor sterilization: definition and importance of R0. J Ind Microbiol 4: 247–252.

    Google Scholar 

  7. Buckland B. 1984. The translation of scale in fermentation processes: the impact of computer process control. Bio/Technol 2: 875–883.

    Google Scholar 

  8. Buckland B, T Brix, H Fastert, K Gbewonyo, G Hunt and D Jain. 1985. Fermentation exhaust gas analysis using mass spectrometry. Bio/Technol 3: 982–988.

    Google Scholar 

  9. Byrne KM, BH Arison, M Nallin-Omstead and L Kaplan. 1993. Biosynthesis of the zaragozic acids. 1. Zaragozic acid A. J Org Chem 58: 1019–1024.

    Google Scholar 

  10. Halleck FE. 1978. Thermal solution sterilization. Pharm Tech 2: 48–54, 64, 66.

    Google Scholar 

  11. Hensens OD, C Dufresne, JM Liesch, DL Zink, RA Reamer and F VanMiddlesworth. 1993. The zaragozic acids: structure elucidation of a new class of squalene synthase inhibitors. Tetrahedron Lett 34: 399–402.

    Google Scholar 

  12. Jain D and BC Buckland. 1988. Scale-up of the efrotomycin fermentation using a computer-controlled pilot plant. Bioprocess Eng 3: 31–36.

    Google Scholar 

  13. Jones CA, PJ Sidebottom RJP Cannell, D Noble and BAM Rudd. 1992. The squalestatins, novel inhibitors of squalene synthase produced by a species ofPhoma. J Antibiot 45: 1492–1498.

    PubMed  Google Scholar 

  14. Thayanithy, K, G Harding and DAJ Wase. 1982. Rearrangement of lactose on sterilization. Biotechnol Lett 4: 423–424.

    Google Scholar 

  15. Wang DIC, CL Cooney, AL Demain, P Dunnill, AE Humphrey and MD Lilly. 1979. In: Fermentation and Enzyme Technology. pp 138–156. Wiley, New York.

    Google Scholar 

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Connors, N., Prevoznak, R., Brix, T. et al. Effects of medium sterilization on the production of zaragozic acids by the fungusLeptodontidium elatius . Journal of Industrial Microbiology 15, 503–508 (1995). https://doi.org/10.1007/BF01570022

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  • DOI: https://doi.org/10.1007/BF01570022

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