1887

Abstract

A high-penicillin-yielding strain of Penicillium chrysogenum was grown in continuous culture on a chemically defined medium with glucose as the growth-limiting component. The cultivations were operated at a constant dilution rate of 0.05 h and the feed concentration of the penicillin V sidechain precursor phenoxyacetic acid was varied between 0 and 6.5 g l. Subsequent formation of penicillin V and by-products related to the penicillin biosynthetic pathway was monitored at steady state. It was established that the concentration of phenoxyacetic acid in the growth medium had to be kept high to obtain a high productivity of penicillin V. The specific production rate of penicillin V as a function of the phenoxyacetic acid concentration followed Michaelis--Menten-type kinetics, from which an overall apparent K value of 42 mM for the incorporation of intracellular phenoxyacetic acid into penicillin V could be obtained. High phenoxyacetic acid concentrations tended to lower the formation of the by-products 6-aminopenicillanic acid and 8-hydroxypenillic acid. Furthermore the undesirable loss of the pathway intermediate isopenicillin N into the extracellular medium was lowered, whereas the opposite effect was observed for the pathway intermediate δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine and the by-product 6-oxo-piperidine-2-carboxylic acid, the δ-lactam form of α-aminoadipic acid.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-144-7-2001
1998-07-01
2021-07-23
Loading full text...

Full text loading...

/deliver/fulltext/micro/144/7/mic-144-7-2001.html?itemId=/content/journal/micro/10.1099/00221287-144-7-2001&mimeType=html&fmt=ahah

References

  1. Alvarez E., Meesschaert B., Montenegro E., Gutiérrez S., Díez B., Barredo J.L., Martín J.F. 1993; The isopenicillin-N acyltransferase of Penicillium chrysogenum has isopenicillin-N amidohydrolase, 6-aminopenicillanic acid acyltransferase and penicillin amidase activities, all of which are encoded by the single penDE gene.. Eur J Biochem 215:323–332
    [Google Scholar]
  2. Christensen L.H., Nielsen J., Villadsen J. 1991; Delay and dispersion in an in-situ membrane probe for bioreactors.. Chern Eng Sci 46:3304–3307
    [Google Scholar]
  3. Christensen L.H., Mandrup G., Nielsen J., Villadsen J. 1994; A rubost LC method for measurement of medium components during penicillin fermentations.. Anal Chim Acta 296:51–62
    [Google Scholar]
  4. Christensen L.H., Henriksen C.M., Nielsen J., Villadsen J., Egel-Mitani M. 1995; Continuous cultivation of Penicillium chrysogenum. Growth on glucose and penicillin production.. J Biotechnol 42:95–107
    [Google Scholar]
  5. Henriksen C.M., Holm S.S., Schipper D., Jørgensen H.S., Nielsen J., Villadsen J. 1997; Kinetic studies on the carboxylation of 6-amino-penicillanic acid to 8-hydroxy-penillic acid.. Proc Biochem 3285–91
    [Google Scholar]
  6. Henriksen C.M., Nielsen J., Villadsen J. 1998; Modelling of the protonophoric uncoupling by phenoxyacetic acid of the plasma membrane potential of Penicillium chrysogenum.. Biotechnol Bioeng in press
    [Google Scholar]
  7. Jørgensen H.S., Nielsen J., Villadsen J., Møllgaard H. 1995; Analysis of the penicillin V biosynthesis during fed-batch cultivations with a high yielding strain of Penicillium chrysogenum.. Appl Microbiol Biotechnol 43:123–130
    [Google Scholar]
  8. Lein J. 1986; The Panlabs penicillin strain improvement program.. In Overproduction of Microbial Metabolites pp. 105–139 Edited by Vanek Z., Hostalek Z. Boston, MA: Butterworths;
    [Google Scholar]
  9. Nielsen J., Villadsen J. 1993; Bioreactors: description and modelling.. In Biotechnology, 2nd edn.. 3 pp. 77–104 Edited by Stephanopoulos G. Weinheim: VCH;
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-144-7-2001
Loading
/content/journal/micro/10.1099/00221287-144-7-2001
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error