Cell factory fermentation process

Apart from new catalytic methods, cascade conversions require new process technologies, such as in situ product recovery, reactor design, and compartmental-ization. In the long term, part of the present-day stoichiometric chemistry as well as bio- and chemocatalytic conversions in multi-step syntheses will gradually be replaced by cascade catalysis in concert, and full fermentations by cell factory design, or combinations thereof (Fig. 13.17). 

Figure 30.12 represents a cell factory model to produce several categories of products via fermentation and biocatalysis processes. Industrial-scale manufacturing aspects such as uses, synthesis methods, and costs of some of these products are reviewed below as well as in Chapter 32. 

There are already several examples of chemicals being produced by microbial fermentation of engineered cell factories, whose production through metabolic engineering has been boosted by the use of genomics tools, e.g., 1,3-propanediol used for polymer production, riboflavin used as a vitamin, and 7-aminodeacetoxy-cephalosporanic acid (7-ADCA) used as a precursor for antibiotics production. Furthermore, in the quest to develop a more sustainable society, the chemical industry is currently developing novel processes for many other fuels and chemicals, e.g., butanol, to be used for fuels, organic acids to be used for polymer production, and amino acids to be used as feed. 

In fact, fermentation is both the oldest and newest type of catalytic processing. In the very old days— back to several thousand years BC— beer, bread and winemaking were t) ical fermentation processes. In the present, modern recombinant DNA technology allows us to reconstruct the cell factories, i.e. the metabolic pathways, and so to develop novel multi-step conversions by fermentation that are not available in nature. 

The essential elements of an integrated bioprocess are as shown in Figure 6.1 (a) feedstock processing capability for the conversion of a wide variety of feedstocks to fermentable carbon and coproduct streams, preferably using enzymes, (b) engineered biocatalysts (cell factories) for the conversion of a variety of carbon substrates... 

Every bioprocess starts with the best possible cell factory. A better performing cell will allow for less capital, lower variable cost for the fermentation, and a simpler recovery process as the product will be more concentrated. More than one property makes for a good cell factory and none of the commonly used cell factories have all the needed attributes. Case-by-case development of a biocatalyst is still the norm, even though a platform for a given organism would help accelerate process development. Described below are elements from a process point of view to consider in choosing a biocatalyst for a bioprocess. 

Black tea—First the leaves are transported from the plantation to the factory as rapidly as possible. The leaves are spread on withering racks and air is blown over the leaves to remove excess moisture. This removes about one-third of the moisture, and the leaves become soft and pliable. After this they are rolled to break the cells and release the juices, which are essential for the fermenting process. Then the leaves are spread out and kept under high humidity to promote fermentation, which develops the rich flavor of black tea, and the leaves become a coppery color. Finally, the leaves are hot-air dried (fired) until the moisture is removed, leaving the leaves brownish black. 

Cadaverine (diaminopentane, DAP), a carbon-5 aliphatic metabolite, is a minor member of the biogenic polyamine family. It owes its trivial name to its first discovery in 1885 during systematic investigation of the putrefaction process of human cadavers [52]. In contrast to DAB, there is no efficient petrochemical production route available, which for a long time hampered its industrial application in the polymer industry. However, several bio-based production processes have meanwhile been developed for DAP production from renewable resources [6, 12, 15-17, 53]. Only recently, Cathay introduced the fully biobased polyamide PA5.10 Terryl , which entered the market in 2015. While the proprietary production process relies on biocatalytic conversion of the rather high-priced fine-chemical lysine, other attempts aim at a fully novo biosynthesis with streamlined cell factories for the direct fermentative production of DAP from cheap conventional fermentation feedstock. For establishing a one-step fermentation process for DAP, the industrial lysine producers E. coli and C. glutamicum were therefore the ideal metabolic chassis. 

Orjuela A, Yanez AJ, Peereboom L, Lira CT, Miller DJ (2011) A novel process for recovery of fermentation-derived succinic acid. Sep Purif Technol 83 31-37 Otero JM, Cimini D, Patil KR, Poulsen SG, Olsson L, Nielsen J (2013) Industrial systems biology of Saccharomyces cerevisiae enables novel succinic acid cell factory. PLoS One 8 1-10 Ponnampalam E (1999) Purification of organic acids using anion exchange chromatography. Patent WO9944707... 

In past years, LAB applications have moved beyond the traditional food fermentation processes to use in delivery of molecules (Martin et al. 2014) and as microbial cell factories for producing value-added products (Boguta et al. 2014). In this chapter the capability of LAB to naturally produce nutraceutics and high value metabolites is discussed the use of recombinant LAB for production of commodity chemicals is presented briefly. 

Biotechnology has had a significant effect on the flavour industry but two factors have limited its application to fragrance. The first is cost, as biotechnological processes are usually quite expensive. The second is selectivity. Individual enzymic reactions are very selective, but biochemical redox reactions require expensive co-factors and so the usual technique is to run whole cell fermentations so as to allow the cell s chemical factory to recycle the co-factors. However, the cell does much chemistry in addition to the reaction we wish it to do and the result is a horrendous effluent problem. In flavours, the problem is often simpler as the whole cell, e.g. a yeast cell, can be used as the product. 

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