Fermentation process development

Metabolic engineering has been intensively studied in the eukaryotic organism Saccha-romyces cerevisiae, which is a model for the biology of eukaiyotic organisms. S. cerevisiae is susceptible to recombinant DNA technology and metabolic engineering is facilitated by the availability of tlie complete genome sequence. 

Die importance of bacteria and eukaiyotic microorganisms is illustrated in Table 7.1, which lists metabolite production by vaiious microorganisms, such as amino acid biosynthesis, ethanol production, lactic acid, and xylitol production, 7-AC A and 7-ADCA-pro-duction. 

In Saccharomyces cerevisiae, substrate extension has been achieved to increase the versatility and improve the economics of S. cerevisiae fermentations. Examples illustrating the extension of substrate range to include Lactose, Malate, Starch and Dextrins, and Xylose are shown in Table 7.2. 

Aspergillus nidulans Enhanced growth rate Overproduction of glyceraldehyde-3-phosphate dehydrogenase increased the specific growth rate in both acetate and glucose in comparison with the parental strain 41 

Clostridium acetobutylicum Acetone and butanol production Overexpression of acetoacetate decarboxylase (adc) and phosphotransbutyrylase (ptb) by introducing a Bacillus subtilis/C acetobutylicum shutde vector into C. acetobutylicum by an improved electrotransformation protocol, which resulted in acetone and butanol formation 88 

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Polysaccharides. Many strains of bacteria produce succinoglycan (1). The Rhizobia, particularly, grow very slowly, and the rate of polymer production is low. Much effort was spent obtaining a strain which produced succinoglycan at a high rate and of good quality (2.3). An organism was selected and a fermentation process developed at laboratory scale. The process has been scaled up successfully and operated at 220 cubic metre scale. 

Neway. J.O. ed. Fermentation Process Development of Industrial Organism. , Marcel Dekker Inc.. New York. NY, 1989. 

In addition, there was always a good collaborative spirit between ourselves in chemical process development and fermentation process development, thanks to excellent rapport with Drs. Richard (Dick) Elander, David Lowe, and Leonardo Cappelletti. 

NPI-0052 is currently manufactured under cGMP through a robust saline fermentation process by S. tropica strain NPS21184. It was quite an effort to find the proper contract manufacturing organisations (CMOs) that would accept and adapt our saline fermentation process, developed in laboratory fermenters, to their industrial-scale production fermenters and also have the proper containment facility to handle the downstream processing (DSP) of the highly potent NPI-0052. 

Schapper D, Aiam M, Szita N, Eliasson Lantz A, Gemaey K (2009) Application of microbioreactors in fermentation process development a review. Anal Bioanal Chem 395(3) 679-695... 

Fonds der Chemischen Industrie, Aminosdu-ren - Bausteine des Lebens (Folienserie 11 des Fonds der Chemischen Industrie), Frankfurt, 1993 R. M. Williams, Synthesis of Optically Active a-Amino Acids, Pergamon Press, Oxford, 1989, Chap. 7, p. 257 I. Shiio, S. Nakamori in Fermentation Process Development of Industrial Organisms (Ed. J. O. Neway), Marcel Dekker, New York, 1989,... 

Fermentation Process Development 197 Table 7.1. Metabolite production by various microrganism [Refs in 502]. 

Sun, Z., Ramsay, J.A., Guay, M. and Ramsay, B.A. (2007) Fermentation process development for the production of medium-chain-length poly-3-hydroxyalkanoates. Applied Microbiology and Biotechnology, 75, 475 85. 

Numerous endeavors have been implemented in fermentation process development in order to alleviate the solvent-induced inhibitory effects and thus improve the fermentation productivity. Usually, the selective removal of fermentation products was integrated simultaneously into the fermentation process in order to maintain a low solvent concentration in the fermentation broth. Many online butanol removal techniques have been reported with various advantages and efficiencies, including liquid-liquid extraction, perstraction, gas stripping, pervaporation, adsorption, reverse osmosis, etc. 

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