Metabolic pathway engineering examples

Another example where metabolic pathway engineering has made a dramatic impact is in the biodegradable polymer field. One of the most widely studied polymers in this family is poly-P-hydroxybutyrate (PHB) (64). A related member of the poly-P-hydroxyalkanoate (PHA) family commercialized by Imperial Chemical Industries (ICI), which later became Zeneca Bio Products,... 

A final example of metabolic pathway engineering is based on polyketide and nonribosomal peptide biosynthesis. Polyketides and nonribosomal peptides are complex natural products with numerous chiral centers, which are of substantial economic benefit as pharmaceuticals. These natural products function as antibiotics [erythromycin A (65), vancomycin (66)], antifungals (rapamycin, amphotericin B), antiparasitics [avermectin Ala (67)], antitumor agents [epothiolone A (68), calicheamicin yj, and immunosuppressants [FK506 (69), cyclosporin A], Because this exponentially growing and intensely researched field has developed, the reader is directed to review articles for additional details.347-359 Also with the potential economic benefit to develop the next blockbuster pharmaceutical, a number of patents and patent applications have been published.360-366... 

Metabolic pathway engineering has numerous applications in food, agriculture, chemical, and pharmaceutical industries. Examples include, but are not limited to, increasing the yield of antibiotics, biosynthetic precursors, or polymers, expanding the metabolic capacity to degrade harmful compounds, or producing novel compounds that cannot be found in nature. 

The list of examples detailed above is by no means exhaustive. Several additional examples of the structure-based control of translation, such as repressor protein binding sequences on the mRNA transcripts and ribozymes [39], are among others that could be listed. The intentions of this chapter are not to enumerate examples of how structural characteristics of mRNA influence its translation. What should be evident from the preceding discussion is that mRNA structure is a critical determinant of translation, and synthetic DNA technology offers the possibility to alter and probe the effects of mRNA sequence on its structure and the resulting translation efficiency. Further developments in this area will be immensely valuable to metabolic engineering as it will enable practitioners to fine-tune the fluxes of desired metabolic pathways through modulation of protein levels. 

Some early attempts at metabolic oligosaccharide engineering using haloge-nated and deoxy sugars resulted in cell death. In retrospect, we now know that some of these compounds are inhibitory of intracellular biosynthetic pathways [37,38], However, the toxicity of halogenated and deoxy sugars could possibly be exploited therapeutically for antiviral, antibacterial, or anticancer therapy. Examples are presented in detail later in this chapter. 

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