Hosts: metabolic engineering

Metabolic Engineering for Overproduction of 6dEB in Heterologous Hosts... 

Besides their essential roles in nature, isoprenoids are of commercial importance in industry. Some isoprenoids have been used as flavors, fragrances, spices, and food additives, while many are used as pharmaceuticals to treat an array of human diseases, such as cancer (Taxol), malaria (artemisinin), and HIV (coumarins). In contrast to the huge market demand, isoprenoids are present only in low abundance in their host organisms. Thus, isolation of the required isoprenoids consumes a large quantity of natural resources. Furthermore, owing to their structural complexity, total chemical synthesis is often not commercially feasible. For these reasons, metabolic engineering may provide an alternative to produce these valuable isoprenoids [88,89]. 

Tao, L., Jackson, R.E. and Cheng, Q. (2005) Directed evolution of copy number of a broad host range plasmid for metabolic engineering. Evolutionary Engineering, 7, 10-17. 

Freitag A, Rapp H, Heide L et al (2005) Metabolic engineering of aminocoumarins inactivation of the methyltransferase gene cloP and generation of new clorobiocin derivatives in a heterologous host. ChemBioChem 6 1411-1418... 

ACV synthetase presents a suitable model system to analyze structure-function relations in NRPS systems [89], Here we have focused on the current state of understanding and interpretation of structure-function relations of ACV synthetases. These aspects are of importance for the future development of nonribo-somal peptide-forming systems, especially in filamentous fungal hosts. Other major aspects of process analysis and metabolic engineering approaches to improve the yield of antibiotic fermentations have not been discussed. These process aspects include the following four approaches. 

The need for novel catalytic processes is clear and, as discussed in Chapter 9, combining catalytic steps into cascade processes, thus obviating the need for isolation of intermediate products, results in a further optimization of both the economics and the environmental footprint of the process. In vivo this amounts to metabolic pathway engineering [20] of the host microorganism (see Chapter 8) and in vitro it constitutes a combination of chemo- and/or biocatalytic steps in series and is referred to as cascade catalysis (see Chapter 9). Metabolic engineering involves, by necessity, renewable raw materials and is a vital component of the future development of renewable feedstocks for fuels and chemicals. 

In addition to metabolic engineering of the specific riboflavin pathway and its immediate supply routes, that is, purine and pentose phosphate pathways, improving of general host properties that relate to the performance under industrial process conditions is mandatory for commercially viable production processes. Industrial... 

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