US 4,062,727 AGranted

Process for manufacturing high density cell cultures

AssigneeLouisiana State University Foundation

InventorsVadake R. Srinivasan, Marvin B. Fleenor, Richard J. Summers, Margaret W. Bumm

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Abstract

A process for biosynthetically producing cells in a liquid fermentation media comprised of a carbon source, and a growth medium containing oxygen and other essential cell nutrients, to obtain a biomass for harvesting. The carbon source and each of the other essential cell nutrients are added, incrementally or continuously, to the fermentation media, and each required nutrient is maintained at essentially the minimum level needed for efficient assimilation by the growing cells, in accordance with a predetermined cell growth curve based on the metabolic or respiratory function of the cells which convert the carbon source to a biomass. The process constitutes a marked improvement in accelerating and increasing cell production in a given fermentation system. In its preferred aspects, the nutrients are added within the fermentation media below the foam level which forms on top of the fermentation broth. A particularly preferred fermentation system embodies the preparation, in a nutrient medium, of comestible, digestible protein from a carbon source, suitably a hydrocarbon or carbohydrate, particularly delignified cellulose. A cellulase-elaborating microorganism, suitably a fungii, yeast or bacteria, particularly a microorganism of the genus Cellulomonas (ATCC-21399) used alone, or in compatible association with another microorganism, is cultivated within the medium which contains the carbon source.

Claims6

Dependent claims

In a process for biosynthetically cultivating cells in an aqueous fermentation medium comprising a carbon source, nitrogen, phosphorus, trace mineral elements, and oxygen in amount sufficient to provide a predetermined oxygen level, to obtain a biomass of such cells for harvesting, the improvement which comprises

adding the carbon source, nitrogen, phosphorus, and each of the trace mineral elements to the fermentation medium, incrementally or continuously, and maintaining each throughout fermentation at essentially the minimum level required for assimilation by the cells to sustain growth, thereby maximizing the cellular growth rate;
said minimum requirements for the carbon source, the nitrogen, the phosphorus and each of the trace mineral elements having been established in accordance with a predetermined cell growth rate curve,
said predetermined cell growth rate curve having been independently established for the carbon source, the nitrogen, the phorphorus, and each of the trace metal elements, at different biomass levels in a continuous culture medium as occurs from the beginning of fermentation to the end of the period of growth of the cells in the fermentation medium, by starving the growing cellular mass of a nutrient, the minimum concentration of which is to be established while all other of the required nutrients are provided in quantity adequate to sustain growth of the cellular mass and, when growth has ceased due to a lack of the particular nutrient of which the cells have been deprived, adding the nutrient in measured incremental concentrations until growth of the cells has resumed.

Dependencies are inferred from the claim text.