Examples from amino acid biosynthetic pathways

Figure 4. Examples of glycolic acids and polyglycolides that can be obtained from amino acid biosynthetic pathways.

Inspection of the amino acid biosynthetic pathways shows that all amino acids arise from a few intermediates in the central metabolic pathways (see fig. 21.1). Amino acids de-rived from a common intermediate are said to be in the same family. For example, the serine family of amino acids, which includes serine, glycine, and cysteine, all arise from glycerate-3-phosphate (see fig. 21.1). The carbon flow from the central metabolic pathways to amino acids is a regulated... 

The shikimate biosynthetic pathway occurs in bacteria, plants, and fungi (including yeasts) and is a major entry into the biosynthesis of primary and secondary metabolites, for example aromatic amino acids, menaquinones, vitamins, and antibiotics [1], Starting from erythrose-4-phosphate (E4P) and phosphoenol-pyruvate... 

Some catabolic reactions of amino acid carbon chains are easy transformations to and from TCA cycle intermediates—for example, the transamination of alanine to pyruvate. Reactions involving 1-carbon units, branched-chain, and aromatic amino acids are more complicated. This chapter starts with 1-carbon metabolism and then considers the catabolic and biosynthetic reactions of a few of the longer side chains. Amino acid metabolic pathways can present a bewildering amount of material to memorize. Perhaps fortunately, most of the more complicated pathways lie beyond the scope of an introductory course or a review such as this. Instead of a detailed listing of pathways, this chapter concentrates on general principles of amino acid metabolism, especially those that occur in more than one pathway. 

In general, biosynthetic pathways (including fuel storage) are referred to as anabolic pathways, that is, pathways that synthesize larger molecules from smaller components. The synthesis of proteins from amino acids is an example of an anabolic pathway. Catabolic pathways are those pathways that break down larger mol-ecnles into smaller components. Fuel oxidative pathways are examples of catabolic pathways. 

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... 

A small number of other biosynthetic pathways, which are used by both photosynthetic and nonphotosynthetic organisms, are indicated in Fig. 10-1. For example, pyruvate is converted readily to the amino acid t-alanine and oxaloacetate to L-aspartic acid the latter, in turn, may be utilized in the biosynthesis of pyrimidines. Other amino acids, purines, and additional compounds needed for construction of cells are formed in pathways, most of which branch from some compound shown in Fig. 10-1 or from a point on one of the pathways shown in the figure. In virtually every instance biosynthesis is dependent upon a supply of energy furnished by the cleavage to ATP. In many cases it also requires one of the hydrogen carriers in a reduced form. While Fig. 10-1 outlines in briefest form a minute fraction of the metabolic pathways known, the ones shown are of central importance. 

In relation with resistance of weeds to herbicides, Duke et al. (2000) mentioned that new mechanisms of action for herbicides are highly desirable to fight evolution of resistance in weeds, to create or exploit unique market niches, and to cope with new regulatory legislation. Comparison of the known molecular target sites of synthetic herbicides and natural phytotoxins reveals that there is little redundancy. Comparatively little effort has been expended on determination of the sites of action of phytotoxins from natural sources, suggesting that intensive study of these molecules will reveal many more novel mechanisms of action. These authors gave some examples of natural products that inhibit unexploited steps in the amino acid, nucleic acid, and other biosynthetic pathways AAL-toxin, hydantocidin, and various plant-derived terpenoids. 

The 10 amino acids essential in the human diet (Arg, His, He, Leu, Lys, Met, Phe, Thr, Trp, Val) are synthesized by non-human organisms by multistep pathways starting from simple metabolic precursors. Amino acid biosynthesis is controlled by feedback inhibition and suppression of synthesis of biosynthetic enzymes. The ability of an amino acid analogue to block biosynthesis of the parent amino acid often contributes to the toxicity of the analogue. Mutants resistant to the toxic effects of the analogue can be valuable tools for studying various aspects of cellular mechanism (examples to be given below). 

Thus far, discussion has focused on the citric acid cycle as the major degradative pathway for the generation of ATP. As a major metabolic hub of the cell, the citric acid cycle also provides intermediates for biosyntheses (Figure 17,19). For example, most of the carbon atoms in porphyrins come from succinyl CoA. Many of the amino acids are derived from a -ketoglutarate and oxaloacetate. These biosynthetic processes will be discussed in subsequent chapters. 

Traditional fermentation using microbial activity is commonly used for the production of nonvolatile flavor compounds such as acidulants, amino acids, and nucleotides. The formation of volatile flavor compounds via microbial fermentation on an industrial scale is still in its infancy. Although more than 100 aroma compounds may be generated microbially, only a few of them are produced on an industrial scale. The reason is probably due to the transformation efficiency, cost of the processes used, and our ignorance to their biosynthetic pathways. Nevertheless, the exploitation of microbial production of food flavors has proved to be successful in some cases. For example, the production of y-decalactone by microbial biosynthetic pathways lead to a price decrease from 20,000/kg to l,200/kg U.S. Generally, the production of lactone could be performed from a precursor of hydroxy fatty acids, followed by p-oxidation from yeast bioconversion (Benedetti et al., 2001). Most of the hydroxy fatty acids are found in very small amounts in natural sources, and the only inexpensive natural precursor is ricinoleic acid, the major fatty acid of castor oil. Due to the few natural sources of these fatty acid precursors, the most common processes have been developed from fatty acids by microbial biotransformation (Hou, 1995). Another way to obtain hydroxy fatty acid is from the action of LOX. However, there has been only limited research on using LOX to produce lactone (Gill and Valivety, 1997). 

Onr diet also must contain the compounds we cannot synthesize, as well as all the basic building blocks for compounds we do synthesize in our biosynthetic pathways. For example we have dietary requirements for some amino acids, but we can synthesize other amino acids from our fuels and a dietary nitrogen precursor. The compounds required in our diet for biosynthetic pathways include certain amino acids, vitamins, and essential fatty acids. 

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