Metabolically engineered cells

The manufacturing processes need to take a holistic view of tlie total life cycle of products including tlieh manufactme and disposal (from factory and from patient). Tlie choice of chual syntheses, metabolically engineered cells, microreactors for optimized processes, and medical devices designed for function and recycling (and manufacturability) are key considerations to be applied early in the development process. 

The manipulation of cellular metabolic pathways in bioreactors is the aim of metabolic engineering. Cells are used that are capable of producing useful biochemicals. However, they often don t produce them in economical qnantities. Changing the genetic machinery of the cell or changing the composition of the bioreactor growth medium can enhance by several hundred percent the amounts of useful products. 

Becker, J. and Wittmann, C. (2015) Advanced biotechnology metabolically engineered cells for the bio-based production of chemicals and fuels, materials, and health-care products. Angew. Chem. Int Ed., 54., 3328-3350. 

It is important that chemical engineers master an understanding of metabolic engineering, which uses genetically modified or selected organisms to manipulate the biochemical pathways in a cell to produce a new product, to eliminate unwanted reactions, or to increase the yield of a desired product. Mathematical models have the potential to enable major advances in metabolic control. An excellent example of industrial application of metabolic engineering is the DuPont process for the conversion of com sugar into 1,3-propanediol,... 

Generation of mutants is also a starting point in optimization experiments, and now is the time for metabolic engineering of the astaxanthin biosynthetic pathway. Researchers should be able to manage carbon fluxes within the cells and resolve competitions between enzymes such as phytoene desaturase and lycopene cyclase. 

Kaup, B., Bringer-Meyer, S. and Sahm, H. (2004) Metabolic engineering of Escherichia coir, construction of an efficient biocatalyst for D-mannitol formation in a whole-cell biotransformation. Applied Microbiology and Biotechnology, 64 (3), 333-339. 

During the last decade, significant advancements in biochemistry, molecular cloning, and random and site-directed mutagenesis, directed evolution of biocatalysts, metabolic engineering and fermentation technology have led us to devise methods to circumvent the disadvantages of whole-cell biotransformation discussed in Section 10.2. The applications of these methods are summarized in this section. 

Metabolic Engineering of Taxol in Plant and Plant Cell Culture... 

Jaluria, P., Betenbaugh, M., Konstantopoulos, K. et al. (2006) Application of microarrays to identify and characterize genes involved in attachment dependence in HeLa cells. Metabolic Engineering, 9, 241-251. 

It is worth mentioning that metabolic engineering of E. coli recently provided recombinant strains which synthesized PHAMCL from gluconate. For this, beside phaC2Po or phaClPa> the thioesterase I from E. coli (TesA) [128] or the acyl-ACP thioesterase from Umbellularia californica [129], respectively, were expressed in E. coli. However, the amounts of PHAMCL accumulated in the cells were rather low, and this artificial pathway was not very efficient. 

Biochemical engineers also have made major contributions to a better understanding of cells, tissues, and organisms. These contributions fall mainly under such categories as metabolic engineering, cellular engineering, and hemodynamics. 

Biosynthetic production of thymidine is overall a complex process combining the controlled introduction of a novel biotransformation step into a biological system with selective enhancement or knock-out of a series of existing metabolic steps. Metabolic engineering to enhance cofactor recycling at both ribonucleotide reduction and dUMP methylation steps has important parallels in other systems, as whole-cell biotransformations are frequently employed as a means to supply, in situ, high-cost and usually labile cofactors. 

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