Synthetic Pathway Modules

The versatility of this synthetic pathway can be illustrated by the ability to modulate the physical properties of the precursor and composition at any of the intermediate synthetic steps by either... 

It has been increasingly appreciated that many chemotherapeutic agents are capable of modulating ceramide metabolism these include doxorubicin, etoposide, ara-C, vincristine, and many others (Table 4). An illustrative example is provided by Fenretinide 4-HPR, a synthetic retinoid that induces p53-independent cytotoxicity in solid tumor cell lines. It was demonstrated that Fenretinide 4-HPR can increase ceramide synthesis through the de novo synthetic pathway and that inhibition of ceramide formation prevents its cytotoxicity (Erdreich-Epstein et al, 2002 O Donnell et al, 2002). 

Precursor balancing and alteration of metabolic fluxes in the central pathways play major roles in the high-level production of metabolites. Redirection of carbon flux from pyruvate to G3P by overexpression of phosphoenolpyruvate synthase and inactivation of competing pathways resulted in improved lycopene production in E. coli [107]. In one study, P-carotene synthetic genes of Pantoea agglomerans were first integrated into the E. coli chromosome. P-Carotene synthetic pathway in recombinant E. coli was then divided into five modules P-carotene synthesis, MEP, and three central metabolic modules. Expression... 

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. 

---