Microorganisms, tryptophan biosynthesis

Anthranilic acid and indole are precursors of tryptophan in numerous microorganisms and fungi (e.g., 5, 263, 264, 602, 741, 783, 785, 816, 854, 855, 876), and it is probable that anthranilic acid is derived, with intermediate steps, from the common precursor, CP of diagram 1. The conversion of anthranilic acid to indole and tryptophan has been shown unambiguously in Neurospora with the use of isotopic techniques (93, 663). There may, however, be other pathways for tryptophan biosynthesis (45, 702). Tryptophan can, for example, be formed by transamination of indolepyruvic acid (e.g., 470, 912), which might be formed other than via anthranilic acid. Thus aromatic-requiring mutants have been found which accumulate unidentified indole compounds (307). 

Tryptophan Biosynthesis. Tryptophan is another of the amino acids required by animals but synthesized only by plants and microorganisms. The synthesis of tryptophan in microorganisms has been outlined in recent years, but some of the reactions are still quite obscure. The known intermediates include shikimic acid, anthranilic acid, and indole. The mechanism of the conversion of shikimic acid to anthranilic acid has not been elucidated. 

We have described reactions from various different pathways in this chapter so far, but now we are going to look at one complete pathway in detail. It is responsible for the biosynthesis of a large number of compounds, particularly in plants. Most important for us is the biosynthesis of the aromatic amino acids Phe (phenylalanine), Tyr (tyrosine), and Trp (tryptophan). These are essentiar amino acids for humans—we have to have them in our diet as we cannot make them ourselves. We gel them from plants and microorganisms. 

Chemical conversions of marcfortine to paraherquamides have been achieved [415]. Utilising various soil-derived microorganisms, individual hydroxylation at carbon atoms 5, 10, 12, 14, 15, 16 and 27 has been realized [416] but no improvement on the activity of (244) was observed. A study of the biosynthesis of (244) has shown that it is derived from methionine, tryptophan, lysine and two isoprene units, the latter two being derived from acetic acid. The pipecolic acid moiety arises from lysine via a-ketoglutarate [417]. 

Plant secondary metabolites are biosynthesized from rather simple building blocks supplied by primary metabolism. Two important metabolic routes in this are the shikimate pathway and the isoprenoid biosynthesis. The shikimate pathway leads to the synthesis of phenolic compounds and the aromatic amino acids phenylalanine, tyrosine and tryptophan. The isoprenoid biosjmthesis is a heavily branched pathway leading to a broad spectrum of compounds (fig. 1). From plants and microorganisms more than 37,000 isoprenoid compounds have been isolated so far [1]. 

Quinoline alkaloids a group of alkaloids based on the quinoline skeleton. They are found both in microorganisms (see Viridicatine) and in higher plants. The most important therapeutically are the Cinchona alkaloids (see). The starting material for the biosynthesis of some Q. a. is anthranilic acid (see Viridicatine) for others it is tryptophan (see Cinchona alkaloids). 

The tryptophan biosynthetic pathway in microorganisms is one of the branches from a common pathway for the biosynthesis of the aromatic substances. Some regulation of tryptophan synthesis occurs at the level of the common aromatic pathway as well as at the level of the synthesis of glutamine [1,2], a tryptophan precursor. This chapter will be... 

For the biosynthesis of cell components a microorganism must be supplied with appropriate low molecular weight compounds such as sugars, organic acids, amino acids etc. Many of 2-, 3-, 4- and 5-carbon compounds are formed in catabolic reactions. In propionic acid bacteria these reactions comprise the propionic acid fermentation, TCA cycle and hexose monophosphate shunt. The latter supplies the cell with erythrose-phosphate, ribose-5-phosphate and reducing equivalents (NADPH) needed for many syntheses. Erythrose-4-phosphate is used in the formation of aromatic amino acids phenylalanine, tryptophane, tyrosine. Ribose-5-phosphate is incorporated into nucleic acids. The pentose cycle and propionic acid fermentation, as mentioned before, have a number of common precursors and enzymes. The inclusion of common precursors into one or another pathway is regulated by the level of ATP (Labory, 1970), and this regulation in fact determines the ratio of catabolic and anabolic processes in the cell. 

The biosynthesis of nicotinic acid in animals and some microorganisms is well established to be by degradation of tryptophan, whereas in plants nicotinic acid has its origins in aspartic acid and glycerol (glyceraldehyde) via quinolinic acid [6.72) (Scheme 6.16). 

The pyridine nucleotide cycle is a series of reactions that are ubiquitous in nature, differing only in the biosynthesis of quinolinic acid. It (quinolinic acid) occurs from tryptophan in animals, fowl, molds, and in certain microorganisms. It may come from either aspartate and glyceraldehyde-3-phosphate in higher plants and bacteria. In other plant systems highly specialized examples exist, such as mimosine, fusaric acid, and actinidine, where other precursors are used. 

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