Chemistry: molecular biology and microbiology – Micro-organism – per se ; compositions thereof; proces of... – Fungi
Patent
1994-10-12
1996-10-08
Rollins, John W.
Chemistry: molecular biology and microbiology
Micro-organism, per se ; compositions thereof; proces of...
Fungi
4352563, 4352565, 4352568, 435929, 435933, C12N 114
Patent
active
055630650
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a process for the continuous or fed batch cultivation of a filamentous microorganism which is controlled to delay or prevent the development of an undesirable variant in the the culture. In particular the invention relates to a process for the production of a proteinaceous product or a metabolite.
During continuous cultivation of filamentous micro-organisms there is a tendency, particularly after prolonged cultivation, for highly branched colonial variants of the micro-organism to appear. Sometimes these variants appear to a limited extent only and do not significantly affect the overall growth of the culture. In other instances however the variants occur to an increasing extent and can eventually become the main microorganism components of the cultures containing them. This tendency has undesirable consequences for commercial fermentations using filamentous microorganisms, particularly fermentations for the production of proteinaceous compositions where it is often desirable to produce filamentous microorganisms having only limited hyphal branching.
Since 1969 a process has been developed in which a strain of Fusarium graminearum (Schwabe) is cultivated in a medium containing wheat starch to produce a proteinaceous product which can be formulated into a high protein food for human consumption. The product of this process has good nutritional properties and can be made into a convincing analogue of fibrous foods such as meat and poultry. This process is described inter alia in GB 1346061; GB 1346062; EP 123434 and by Trinci et al in Chapter 2 of "Microbial Growth Dynamics", edited by R K Poole et al and published by the Society of General Microbiology the contents of which documents are incorporated herein by reference. It is desirable that the cultivation conditions are controlled to produce restricted branching of the filamentous product and to limit the extent to which undesirable colonial variants of the process micro-organism develop in the culture.
We have now developed a means whereby a continuous cultivation of a filamentous microorganism can be controlled to delay or prevent the development of an undesirable variant in the culture.
According to the present invention we provide a process for the cultivation in continuous culture of a filamentous microorganism in a culture medium to which are supplied sources of appropriate nutrients including carbon, are nutrient source being supplied in an amount limiting to the growth of the culture and constituting a limiting nutrient thereto, wherein development of an unwanted variant of the filamentous microorganism is restricted and/or declared by supplying a first nutrient source to the culture as a limiting nutrient and then changing the nutrients supply to the culture in a manner such that a second nutrient source replaces the first nutrient source as the limiting nutrient.
Further according to the present invention we provide a process for the production of a proteinaceous product by cultivation in continuous culture of a filamentous microorganism in a culture medium to which are supplied sources of other appropriate nutrients including carbon. One nutrient source being supplied in an amount limiting to the growth of the culture and constituting a limiting nutrient thereto, and separation of the filamentous microrganism from the culture wherein development of an unwanted variant of the filamentous microorganism is restricted and/or delayed by supplying a first nutrient source to the culture as a limiting nutrient and then changing nutrients supply to the culture in a manner such that a second nutrient source replaces the first nutrient source as the limiting nutrient.
Further according to the present invention we provide a process for the production of a metabolite by cultivation in continuous or fed batch culture of a filamentous microorganism in a culture medium to which are supplied sources of carbon and other appropriate nutrients, the carbon or another nutrient source being supplied in an amount limiting to the growth of the
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Robson Geoffrey D.
Trinci Anthony P. J.
Wiebe Marilyn G.
Rollins John W.
Zeneca Limited
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