Production strains

It is increasingly evident that even when an efficiendy expressed gene is inserted into a suitable host, the optimal production strain is rarely obtained. Among the properties that may need to be improved are genetic and product stabiUty. 

Commercial fermentation groups usually maintain different strains of cultures suitable for production so that phage attacks can be thwarted by substituting a nonsusceptible culture. After a period of time for the phage to dissipate, it may be possible to return the most desirable production strain. 

In a good production strain, the plasmid should be present in a stable way and should not be lost from the micro-organism after a few generations. 

For economical reasons the fermentation time should be as short as possible with a high yield of the amino acid at the end. A second reason not to continue the fermentation in the late stationary phase is the appearance of contaminant-products, which are often difficult to get rid off during the recovery stage. In general, a relatively short lag phase helps to achieve this. The lag phase can be shortened by using a higher concentration of seed inoculum. The seed is produced by growing the production strain in flasks and smaller fermenters. The volume of the seed inoculum is limited, as a rule of tumb normally 10% of the fermentation volume, to prevent dilution problems. 

Back mutation (reversion) of the mutant production strain to the wild type (prototrophic form) can occur. 

From this one ancestral fungus each penicillin manufacturer has evolved a particular production strain by a series of mutagenic treatments, each followed by the selection of improved variants. These selected variants have proved capable of producing amounts of penicillin far greater than those produced by the wild strain, especially when fermented on media under particular control conditions developed in parallel with the strains. These strain selection procedures have become a fundamental feature of industrial biotechnology. 

Production strains are stored in a dormant form by ai r of the standard culture preservation techniques. Thus, a spore suspension may be mixed with a sterile, finely divided, inert support and desiccated. Alternatively, spore suspensions in appropriate media can be lyophilized or stored in a hquid culture biostat. 

The P. patens system is being developed by the German biotechnology company Greenovation Biotech GmbH, which is based in Freiburg. The company has developed transient expression systems that allow feasibility studies, and stable production strains that can be scaled up to several thousand liters. 

To the extent that cyclic transition-state strains parallel ring-product strains, the above considerations provide a proper guideline for prediction and interpretation of the oxygen-atom effect on rates of ring closure. This is clearly shown by a comparison of EM data for the two closely related ring-closure reactions (43) and (53a) in 75% aqueous ethanol (Illuminati et... 

Collection and selection of potentially high productivity strains from various environment... 

CGTase Production. Strain ATCC 53627 was cultured for 40 hours at 70 C in a prereduced liquid medium under argon at pH 7.0 comprised of the following components in grams/liter Maltrin M-lOO, 5.0 KH9PO4,2.0 K2HPO4, 6.0 NaCl, 1.0 ... 

The problem with marine natural products is the scarce availability. A measure of the problem is given by bryostatin 1, a promising antitumor macrolide recomse to ejqiensive cultures of the productive strain of bryozoan on 1 m panels on the open sea off the Californian coast was the only... 

By market volume the most important flavour molecule is L-glutamic acid. In 2004, the worldwide annual MSG production was estimated to be amount 1,500,0001 [21]. The amino acid is extensively used as taste enhancer, frequently in conjunction with nucleotides, a flavour impression which is also referred to as umamf, a term derived from the Japanese meaning deliciousness or a savoury or palatable taste. MSG is manufactured by aerobic cultivation of Coryne-bacterium glutamicum on starch hydrolysates or molasses media in large-scale bioreactors (up to 500 m ). Production strains with modified metabolic flux profiles and highly permeable cell walls for an improved product secretion are... 

Metabolite Production. Strain variations to hexobarbital are often dependant on its degradation rate. For example, male mice of the AL/N strain are long sleepers, and this trait is correlated with slow inactivation of the drug. The reverse is true in CFW/N mice, which have short sleeping time due to rapid hexobarbital oxidation. This close relationship is further evidenced by the fact that the level of brain hexobarbital at awakening is essentially the same in all stains. Similar strain differences have been reported for zoxazolamine paralysis in mice. 

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