Fermentation optimisation

Fermentation optimisation has been used for a long time to increase the yield and productivity of many bioprocesses [20]. Optimisation refers to obtaining the maximum benefit by improving the performance of a system, process or product [21]. Optimisation involves finding a critical value for each factor that satisfies the response. Previonsly, optimisation has been used extensively in analytical applications, bioprocesses and industry [22]. 

For the industrial production of riboflavin as pharmaceuticals, the traditional methodology comprising the dkect condensation of (13) with (14) in an acidic medium with continuous optimisation of the reaction conditions is stiU used (28). A great part of riboflavin manufactured by fermentative methods is used for feeds in the form of concentrates. The present world demand of riboflavin may be about 2500 t per year. Of this amount, 60%, 25%, and 15% are used for feeds, pharmaceuticals, and foodstuffs, respectively. The main producers are Hoffmann-La Roche, BASF, Merck Co., and others. 

The content of desired enzymes at the end of fermentation processes should be as high as possible in order to ease the downstream processing. This may be achieved by a proper choice of microorganisms, optimising the fermentation conditions (e.g. culture media, inducer, morphology, growth rate) or by RDNA technology. 

Bories, A., Himmi, E.H., Jauregui, J.J.A., Pelayo-Ortiz, C. and Gonzales, V.A. 2004. Glycerol Fermentation with Propionibacteria and Optimisation of the Production of Propionic Acid. Sciences des Aliments, 24, 121-135. 

While these examples illustrate the role of flow cytometry in bioprocess monitoring, the analyses have been conducted off-line thus making their use in bioprocess control impractical. Recently, a portable flow cytometer - the Microcyte - [148] has been described, which due to its small size and lower cost (compared to conventional machines) allows flow cytometry to be used as an at-line technique [149]. Ronning showed that this instrument had a role to play in the determination of viability of starter cultures and during fermentation. The physiological status of each individual cell is likely to be an important factor in the overall productivity of the culture and is therefore a key parameter in optimising production conditions. 

This intensive optimisation of production from shake flask to laboratory-scale fermenter provided the foundation for a smooth transition to large-scale manufacturing of the drug substance, as discussed in Section 7. 

ID Reid. Optimisation of solid-state fermentation for selective delignification of aspen wood with Phlebia tremellosa. EnzMicrob Technol 11 804—809, 1989. 

The fermentative production of vanillin is elegant, and with future optimisation and improvements at various stages, it may still have the chance to become the basic pillar of a fourth generation of industrial vanillin syntheses. 

For the preparation of pravastatin (Mevalotin , Sankyo), at first mevastatin is obtained from fermentation of Penicillium citrinum its regio- and stereo-selective enzymatic hydroxylation can be achieved with a number of different microbial strains Mucor hiemalis, Penicillium coccineus, Rhizoctonia solani or Nocar-dia. Streptomyces carbophilus is used today to produce mevastatin under optimised conditions a productivity of around 5 g/1 or even higher can be obtained. [392]... 

Although the biosynthesis of PHA from wastewater offers an interesting alternative to the pure culture, high-cost sugar-based PHA production, the PHA yields reported are not yet comparable to the petrochemical counterparts. Integration and optimisation need to be considered further to improve the performance of wastewater fermentability in PHA production [6]. 

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