The Biosynthetic Pathways

J.E. Baldwin (1975, 1976A) has developed a biomimetic synthesis which is loosely analogous to the biosynthetic pathway which starts with the so-called Amstein tripeptide. Baldwin used bicyclic dipeptides more suitable for stereoselective in vitro syntheses. 

These organisms have been used frequently in the elucidation of the biosynthetic pathway (37,38). The mechanism of riboflavin biosynthesis has formally been deduced from data derived from several experiments involving a variety of organisms (Fig. 5). Included are conversion of a purine such as guanosine triphosphate (GTP) to 6,7-dimethyl-8-D-ribityUuma2ine (16) (39), and the conversion of (16) to (1). This concept of the biochemical formation of riboflavin was verified in vitro under nonen2ymatic conditions (40) (see Microbial transformations). 

In contrast to vitamin K, there has been considerably more activity on fermentative approaches to vitamin (50). The biosynthetic pathway to vitamin K2 is analogous to that of vitamin except that poly(prenylpyrophosphates) are the reactive alkylating agent (51,52). Menaquinones of varying chain lengths from to have been isolated from bacteria. The most common forms are vitamin K2 35, (40) (45) significant amount of K2 20)... 

Cb) Show the mechanism of each step in the biosynthetic pathway, using curved arrows to indicate electron flow. 

All the essential monosaccharides arise from glucose, by the conversions summarized in Figure 25.10. We ll not look specifically at these conversions, but might note that end-of-chapter Problems 25.55 through 25.57 lead you through several of the biosynthetic pathways. 

The biosynthetic pathways for sterol biosynthesis have been known for a long time and a brief summary is presented in Scheme l.3 Starting from acetyl CoA (2), acetoacetyl CoA, and... 

More frequently, however, mutation is used to block a particular pathway. Streptomyces fradiae produces neomycin. 2-Deoxystreptamine is an intermediate in the biosynthetic pathway leading to the production of neomycin (see Figure 6.20). 

The small overproduction of amino adds by wild type strains in culture media is the result of regulatory mechanisms in the biosynthetic pathway. These regulatory mechanisms are feedback inhibition and repression. 

Auxotrophic mutants are mutants that miss one or more of the enzymes used in the biosynthetical pathway for one or more amino adds. In practice this means that the mutant needs one or more key metabolites which it cannot synthesise for growth in its growth medium. For example, consider Figure 8.4. 

Isoprenoids are intermediates and products of the biosynthetic pathway that starts with mevalonate and ends with cholesterol and other sterols. 

NifH and NifDK to GroEL. It is not clear from these data at which stage in the biosynthetic pathway just described GroEL might be involved in MoFe protein maturation, but it could be during P cluster insertion. 

As 2-amino-2-deoxy-D-mannose is tumorstatic and 2-acetamido-2-deoxy-D-mannose 6-phosphate is an obligatory intermediate in the biosynthetic pathway to sialic acid, displacement of the essential OH-6 with a fluorine atom should be interesting from the biological viewpoint. 2-Acetamido-1,3,4-tri-0-acetyl-2,6-dideoxy-6-fluoro-D-mannopyranose (see Table 111 in Section 11,3) and its O- and A,0-deacetyl derivatives were prepared the first compound showed weak anticancer activity. 

The conversion of tyrosine to epinephrine requires four sequential steps (1) ring hydroxylation (2) decarboxylation (3) side chain hydroxylation to form norepinephrine and (4) N-methylation to form epinephrine. The biosynthetic pathway and the enzymes involved are illustrated in Figure 42-10. 

Shimizu et al. (56) studied the biosynthesis of the STX analog neoSTX using Aph, flos-aquae NH-1. They were able to confirm its presence in strain NH-1 and to explain the biosynthetic pathway for this important group of secondary chemicals. 

By the addition of different acyl donors to the medium, different penieillins can be biologically synthesized. For example, penicillin V is made by a similar process to benzylpenieillin, but with phenoxyacetic add as the precursor instead of PAA. In the biosynthetic pathway, the a-aminoadipyl side-chain of isopeniciUin N is replaced by a phenoxyacetyl group. 

Nonomnra, Y. et al.. Spectroscopic properties of chlorophylls and their derivatives inflnence of molecnlar stmctnre on the electronic state, Chem. Phys., 220, 155, 1997. Blairkenship, R.E., Identification of key step in the biosynthetic pathway of hacteri-ochlorophyU c and its implications for other known and nirknown green sulfur bacteria, J. Bacterial., 186, 5187, 2004. 

Gandia-Herrero, R, Escribano, J., and Garci a-Carmona, R, Betaxanthins as substrates for tyrosinase an approach to the role of tyrosinase in the biosynthetic pathway of betalains. Plant Physiol, 138, 421, 2005. 

Hajjaj, H. et al.. The biosynthetic pathway of citrinin in the filamentous fungi Monascus ruber as revealed by C-NMR, Appl. Env. Microbiol, 65, 311, 1999. Hajjaj, H. et al.. Medium-chain fatty acids affect citrinin production in the filamentous fungus Monascus ruber, Appl. Env. Microbiol, 66, 1120, 2000. 

However, if we can design some sophisticated routes to generate carbanion equivalents in the active site of the enzyme, carboxylation reaction might be possible. In fact, acetyl-CoA is carboxylated with the aid of biotin in the biosynthetic pathway of long-chain fatty acids. 

In spite of the recent progress in understanding the biosynthesis of the major building blocks of proanthocyanidins, (-l-)-catechin and (-)-EC, some important questions still remain to be elucidated (e.g., the exact nature of the molecular species that undergo polymerization and the mechanisms of assembly). The biosynthetic pathways for proanthocyanidins have been extensively reviewed [23-28]. A general scheme summarizing proanthocyanidin biosynthesis adapted from [27] and [28] is reported in Fig. 5. 

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