Secondary metabolic pathways

Application of Isotopic Methods to Secondary Metabolic Pathways T.J. Simpson... 

The activity of PK and NRPSs is often precluded and/or followed by actions upon the natural products by modifying enzymes. There exists a first level of diversity in which the monomers for respective synthases must be created. For instance, in the case of many NRPs, noncanonical amino acids must be biosynthesized by a series of enzymes found within the biosynthetic gene cluster in order for the peptides to be available for elongation by the NRPS. A second level of molecular diversity comes into play via post-synthase modification. Examples of these activities include macrocyclization, heterocyclization, aromatization, methylation, oxidation, reduction, halogenation, and glycosylation. Finally, a third level of diversity can occur in which molecules from disparate secondary metabolic pathways may interact, such as the modification of a natural product by an isoprenoid oligomer. Here, we will cover only a small subsection of... 

Plants produce an amazing diversity of secondary metabolites that not only play important biological roles in their adaptation to environments but also provide humans with dyes, flavors, drugs, fragrance, and other useful chemicals. However, many of the secondary metabolic pathways are found or are amplified only in limited taxonomic groups. In addition, the compounds are often restricted to a particular... 

An attractive hypothesis is the independent evolution in bacteria of their diffusible individualites and the currently recognized secondary metabolic pathways, in parallel with their surface components and their biosynthesis. An indicator for this would be the use of the same gene pool. The theory would include all substances that play a role in the build-up of glycan and other modified surface layers, lipids, murein, (glyco-) proteins (e.g., S-layers), polysaccharides, teichoic... 

The true biochemical significance of this deamination, and the function of the secondary metabolic pathway originating from L-phenylalanine (6-... 

Tenser T, Gee DR. [2005). Modelling the evolution of secondary metabolic pathways. University of York, MPhil Project Report Abstract). Plants and microbes invest heavily in producing chemicals termed Natural Products. These chemicals are produced in secondary metabolic pathways. In this report, we develop a model for the evolution of secondary pathways, and investigate what factors are important in aUowing these pathways to arise and persist. The results imply that certain mutation rates are important in generating chemical diversity, and we give conditions on these for optimal fitness in a population. We also find that the rate of competitive evolution and the chances that new compounds have to be beneficial or harmful are important factors. 

Zaleplon is primarily metabolized by aldehyde oxidase and use with inhibitors of this enzyme, such as cimetidine, may result in increased plasma concentrations of zaleplon. Zaleplon is also partly metabolized by the cytochrome P450 isoenzyme CYP3A4 and, consequently, caution is advised when zaleplon is given with drugs that are substrates for, or potent inhibitors of, this isoenzyme. Cimetidine is also an inhibitor of CYP3A4 and thus inhibits both the primary and secondary metabolic pathways of zaleplon. Use with rifampicin or other potent enzyme-inducing drugs may accelerate the metabolism of zaleplon and reduce its plasma concentrations [40]. 

Viral particle production from cell cultures has several differences from other bioprocesses. The production of molecules like enzymes, toxins, or other proteins synthesized by bacteria, fungi or animals, depend upon culture parameters, such as pH, temperature, dissolved oxygen, or nutrients. Product formation may occur through secondary metabolic pathways, which are not related to the development or growth of the cell. In these situations, research and technological development must be directed to the specific cell and this involves the improvement of the cell as a better molecular production unit. So, there is a direct relation between nutrient conversion, cell growth, and the expected improvement of the final productivity. 

Viral particle production processes by cell culture infection, cannot be characterized in such a simple way, since the final product - virus -does not result from a secondary metabolic pathway. However, it can be better described as a process redirecting the cell machinery towards viral particle production, which only happens after viral infection. The virus production process can be divided into two different steps. The first involves cell multiplication, which results from the conversion of culture medium substrates into cell mass. At the instant of viral infection, the cellular production unit no longer exists, since the viral genetic material forms a new production unit, initiating the second step of the virus production process. This production unit is the infected cell and is the producer of new viral particles. This production phase requires nutritional and metabolic conditions that are not observed during cell growth. These conditions are normally studied separately. Nevertheless, virus production... 

Besides the engineering of S. cerevisiae for organic acid production, through metabolic engineering it is possible to reconstruct entire pathways. In 1994, Yamano et al. [163] reported the reconstruction of a complete secondary metabolic pathway in S. cerevisiae, resulting in the ability of the yeast to produce p-carotene and lycopene. Carotenoids are a class of pigments used in the food industry and, due to their antioxidant properties, they have wide commercial interest. The biosynthesis of these compounds does naturally not occur in S. cerevisiae and to allow... 

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