Proposed biosynthesis pathway

Interestingly, the conversion of 3-dehydro-24-e/ i-teasterone to 24-epi-teasterone follows the opposite direction of the proposed biosynthesis pathway. Feeding experiments support this observation Exogenously applied 3-dehydro-24-e/ /-teasterone was converted to 24-epj-teasterone as the major metabolite (95%), and to only traces (5%) of 24-epi-typhasterol [23]. Thus, it is very likely that there is a different pathway in tomato cell cultures. In addition, preliminary studies with protein extracts of Arabidopsis cell cultures also reveal differences in enzyme distribution and specificity depending on the origin of the culture [Winter, unpublished]. 

In the proposed biosynthesis pathway of wybutosine, the acp-transfer step is catalyzed by Tyw2, which has similarity to methyltransferases that catalyze nucleophilic methyl-transfer reactions (Figure 1.11). 

Scheme 18.2 A proposed biosynthesis pathway of psilocybin biological activities...

Several studies have investigated the biosynthesis of caffeine in tea. The results of a study by Suzuki and Takahashi27 30 suggest a pathway for caffeine biosynthesis in tea from 7-methylxanthine to theobromine and then to caffeine. Additionally they suggest that theophylline is synthesized from 1-methylxanthine. Another study by Ogutuga and Northcote31 proposes a pathway through 7-methylxanthosine to theobromine followed by caffeine. 

Griseofulvin is biosynthetically manufactured by elaboration with Penicillium griseofulvum and related strains of Penicillia. The biosynthesis has been the subject of numerous chemical and biological studies, the latest of which is given by Harris, et. al. (9) Figure 10. Other proposed biosynthetic pathways are discussed. 

The Biosynthetic Pathway for APR. Earlier attempts to propose an APR biosynthesis pathway on the basis of biogenetic studies are scarce. Labeling... 

There are a number of studies on the biosynthesis of various pteridines, i.e., xanthopterin (65), isoxanthopterin (67), erythropterin (73), leucopterin (68), and pterin (62) (509-511). The most important intermediate of the proposed biosynthetic pathway from guanosine triphosphate (GTP) (604) seems to be di-hydroneopterin triphosphate (H2-NTP) (605), however, because evidence has recently been accumulated indicating that pteridines such as biopterin (70), sepiapterin (81), and drosopterins (87) are synthesized from GTP (604) by way of H2-NTP (605) (Scheme 76) (5/2). 

The structural similarity between arsenobetaine and glycine betaine suggested that arsenic may substitute for nitrogen in pathways of phospholipid biosynthesis and was the basis for a proposed biogenetic pathway for arsenobetaine (174). The proposed pathway begins with arsenic present as either arsenoethanolamine or arsenocholine. However, the origin of these two compounds is not discussed, and there has been no experimental evidence to support the hypothesis. 

Fig. 15. Proposed biosynthetic pathways for PUFA biosynthesis in an arachidonic acid-producing fungus, M. alpina 1S-4 Broken arrows show by-paths through which co9 fatty acids and nonmethylene-interrupted PUFAs are formed by mutants of M. alpina 1S-4, Mut48 and Mut49, respectively. An, An desaturation EL, elongation...

The co-occurrence of these three methoxypyrazines is consistent with a biosynthetic pathway (Figure 2) proposed over 20 years ago 14), The amino acid leucine is envisaged as the source of the C4 side chain of the methoxypyrazine, through condensation of its amino amide with an unspecified C2 component, and methylation of the initial pyrazinone condensation product. This proposed biosynthetic pathway readily accommodates all three methoxypyrazines through incorporation of either leucine, isoleucine or valine, all of which are commonly available amino acids in plants. Although the validity of this pathway in vines or other plant material is unknown, the major features of this proposed pathway have been shown to apply to the biosynthesis of isopropylmethoxypyrazine by certain bacteria (75, 16). 

Alkaloid metabolism in lupine was proved by Wink and Hartmann to be associated with chloroplasts (34). A series of enzymes involved in the biosynthesis of lupine alkaloids were localized in chloroplasts isolated from leaves of Lupinus polyphylls and seedlings of L. albus by differential centrifugation. They proposed a pathway for the biosynthesis of lupanine via conversion of exogenous 17-oxosparteine to lupanine with intact chloroplasts. The biosynthetic pathway of lupinine was also studied by Wink and Hartmann (35). Two enzymes involved in the biosynthesis of alkaloids, namely, lysine decarboxylase and 17-oxosparteine synthetase, were found in the chloroplast stoma. The activities of the two enzymes were as low as one-thousandth that of diaminopimelate decarboxylase, an enzyme involved in the biosynthetic pathway from lysine to diaminopimelate. It was suggested that these differences are not caused by substrate availability (e,g., lysine concentration) as a critical factor in the synthesis of alkaloids. Feedback inhibition would play a major role in the regulation of amino acid biosynthesis but not in the control of alkaloid formation. 

Evidence for such a modular pathway has been provided from studies into the biosynthesis of the polyketide backbone 77 of (41 )-4-[(E)-2-butenyl]-4-methyl-L-threonine 78 which is incorporated into cyclosporin A in Tolypo-cladium niveum [117]. The proposed biosynthesis of 77 is presented in Scheme 29. In vitro studies using a cell extract have verified unambiguously that the biosynthetic mechanism is processive, that the first PKS free intermediate is the tetraketide 79, and that methylation unequivocally occurs at the stage of the enzyme bound 3-oxo-4-hexenoic acid thioester 80 which is the triketide product from the second elongation cycle. These and other results indicate that the methyl transferase activity is inherent in the second module of the putative PKS. 

Not all fungal tetronic acids are derived by this pathway. The biosynthesis of multicolic acid (6.17), a metabolite of P. multicolor, has been shown by carbon-13 labelling experiments to follow entirely a polyketide pathway. The proposed biosynthetic pathway (Scheme 6.2) involves the intermediacy of a 6-pentylresorcylic acid (6.16) and the cleavage of an aromatic ring. 

Fig. 4. Proposed branched pathway for biosynthesis of mammalian GPl anchors. Abbreviations as in Fig. 3. Acylation of inositol ring is indicated by (acyl). EP, phosphoethanolamine. (Redrawn from ref [85].)...

The biosynthetic source of the pyridone ring of 87 was investigated [260]. Thymine was found to inhibit uracil catabolism and 87 biosynthesis by Nocardia lactamdurans this inhibition was reversed by uracil catabolites. Both [5,6-3H]-uracil and [4,5-13c]-uracil were incorporated, with both labelled carbons of the latter being incorporated as a unit at C(4) and C(5) of 87. The proposed biosynthetic pathway (Scheme 2) involved catabolism of uracil to p-alanine, which was then incorporated into the pyridone ring of 87 [260]. 

A certain bacterium can grow with ethanol as its only source of energy and carbon. Propose a pathway to describe how ethanol can enter a pathway that would allow ATP production and synthesis of precursors for biosynthesis. 

The extreme sensitivity of ALA-D to divalent Pb ions has resulted in the measurement of its activity, as an indirect measurement of Pb in human blood (Berlin et al., 1977). Of all the enzymes involved in the hem biosynthesis pathway, it is the one which has been most studied due to the inhibiting effect that Pb has on its activity and the practical importance of the measurement of the enzymatic activity of ALA-D is considered to be of interest as a bioanalytic marker of environmental exposure to P b. This has been assisted by the development of a method which has been standardised at the proposal of the executive council of the European Union. Hemberg Nikkanen (1972) have published an extensive report on the biological meaning of ALA-D inhibition and its use as an exposure test. 

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