Hypothetical biosynthetic pathway

Based on the chemical structures of the isolated norlignans, several hypothetical biosynthetic pathways were proposed [16-18], All these proposed pathways involved coupling of two phenylpropanoid monomer units followed by a loss of one carbon atom to give rise to norlignans. Although this mechanism seemed plausible, another mechanism that involved the addition of two carbon atoms to flavonoid compounds (C6-C3-C6) to give norlignans (Ce-Cs-Ce) could not be mled out. 

Figure 2.7. A hypothetical biosynthetic pathway for KAS (according to Ikeno et al. 2002) °, modified. Abbreviations GA, glucosamine for further explanations see legend to Figure 2.3.

Scheme 5. Various Glycosyltransfer Reactions Related to the Biosynthesis of Glycosphingolipids having Globo-series Sugar Chains. (Broken arrows indicate the hypothetical, biosynthetic pathway.)...

Scheme 66. Hypothetical biosynthetic pathway leading to the phenanthroviridin aglycon (277), the jadomycins (275, 276) and the kinamycin family, e.g., kinamycin F (286). The biosynthetic key step is the oxidative 5,6-bond fission, presumably from dehydrorabelomycin (275) to 285...

Figure 3 shows hypothetical biosynthetic pathway of brassinolide. Namely campesterol or its analogs will be converted to teasterone via several steps of oxidation, then successively oxidized to typhasterol, castasterone and brassinolide. In parentheses, biological activities in the rice lamina inclination assay are shown. The... 

Scheme 3.- Hypothetical biosynthetic pathway to iridoids in Myxopyreae...

Scheme 19. Hypothetical biosynthetic pathway to the pulvinone nucleus...

Fig. 6. Proved and hypothetical biosynthetic pathways for two groups of secoanthraquinones from anthraquinones.

In a branched biosynthetic pathway, the initial reactions participate in the synthesis of sevetal products. Figure 9—4 shows a hypothetical btanched biosynthetic pathway in which cutved attows lead from feedback inhibitors to the enTymes whose activity they inhibit. The sequences S3 —> A, S4 —> B, S4 —> C, and S3 — > D each represent hneat teaction sequences that are feedback-inhibited by theit end products. The pathways of nucleotide biosynthesis (Chaptet 34) provide specific examples. 

The Indo-Pacific sponge Strcmgylophora durissima is noteworthy as it contains essentially one sterol, (24R)-24-ethyl-27-methylcholesta-5,25-dien-3/ -ol (strongylosterol, 63). Four possible biosynthetic routes to this unconventional sterol have been proposed [41-44]. Incorporation experiments with ten radiolabeled precursors were carried out, which demonstrated that only one of the four hypothetical biosynthetic routes is operational. As summarized in Scheme 9 [44], this pathway involves three successive bioalkylations of desmosterol (34), codisterol (52) and 24(28)-dehydroaplysterol (64). No stereoselectivity at C-25 was observed, yet high selectivity at C-24 was found, as epicodisterol (51) was not metabolized. 

The classical progestins as well as the corticosteroids arc based on a steroid nucleus that incorporates a two-carbon side chain at the 17 position that often includes a carbonyl group at position 21. The hypothetical parent hydrocarbon has been assigned the name pregnane for purposes of nomenclature. While two classes of compounds, progestins and corticoids, share common biosynthetic pathways, their biological activities differ markedly. 

An early emergence of adenylate-forming enzymes can also explain the wide diversification of this family of enzymes [175], many of which are now capable of reacting with carboxylic acids without a-amino group (essential in the hypothetical early mechanism using NCAs as substrates, but then useless) and which is involved in many different biosynthetic pathways. 

Administration of triply, 3C-labelled (5)-reticuline to a stable variant non-alkaloid producing cell culture line of Thalictrum tuberosum in cell culture demonstrated a very high incorporation of label into protoberberine alkaloids that were subsequently produced. Since this cell line does not produce reticuline, because the cell line lacks or has insufficient quantities of three methyltransferases that lead to the formation of reticuline, cell cultures that contain this cell line are appropriate for the study of biosynthetic studies., 3C NMR spectroscopy and CIMS were utilized to follow the time course of the metabolism, and demonstrated the rapid formation of scoulerine as a primary reaction product, followed by further tetrahydroprotoberberines and dehydroprotoberberines. The apparently reversible formation of dehydroscoulerine in significant amounts was interpreted as evidence for the role of this compound as an alkaloidal storage product from which scoulerine may be regenerated via enzymic reduction. Scoulerine, dehydroscoulerine, columbamine, and (S)-reticuline were detected by l3C NMR in the crude extracts, while berberine was detected by HPLC. The biosynthetic pathway of these protoberberines in this variant cell culture were summarized as follows [151] (S)-reticuline > scoulerine -> tetrahydrocolumbamine (hypothetical) -> columbamine -> dehydroscoulerine -> candadine -> berberine. 

Figure 1 The retrobiosynthetic principle. Labeling patterns of central metabolic intermediates (shown in yellow boxes) are reconstructed from the labeling patterns of sink metabolites, such as protein-derived amino acids, storage metabolites (starch and lipids), cellulose, isoprenoids, or RNA-derived nucleosides. The reconstruction is symbolized by retro arrows following the principles of retrosynthesis in synthetic organic chemistry. The figure is based on known biosynthetic pathways of amino acids, starch, cellulose, nucleosides, and isoprenoids in plants. The profiles of the central metabolites can then be used for predictions of the labeling patterns of secondary metabolites. In comparison with the observed labeling patterns of the target compounds, hypothetical pathways can be falsified on this basis.

When dealing with transgenic plants one should take into account the potential existence of a plant cytokinin-biosynthetic pathway different from the bacterial ipt encoded pathway. This hypothetical pathway may participate in the accumulation of cytokinins in transformed plants however, this is generally ignored. 

Lupinus termis and related species accumulate a group of alkaloids possessing an unusual carbon skeleton, albine-type bases. In L. termis, (-)-albine (88) co-existed with (-)-multifloriiie (56), (-)-13a-hydroxymultiflorine (82) and (-)-ll,12-seco-12,13-didehydromultiflorine (83). The hypothetical biosynthetic mechanism is proposed to explain the substitution pattern of the propenyl side chain of 88 in relation to the coexistence of 82 and 83 (Fig. 8). In this proposed pathway, aza-Cope rearrangement is involved as the key step for formation of the allylic side chain at the unusual position, C-13. 83 can also be derived from the same pathway of biosyntliesis (84 83). This... 

The biosynthesis of [6]-gingerol was investigated by administration of labelled precursors to whole Z. officinale plants [303, 305]. The hypothetical intermediates [6]-dehydrogingerdione (335), [6]-gingerdione (337) and [6]-dehydrogingerol (339), were synthesized and shown to be incorporated into [6]-gingerol [304]. A biosynthetic pathway for [6]-gingerol was then proposed as shown in "Fig. (4)". 

Figure 4.5 Proposed biosynthetic pathway of polyoximic acid from L-isoleucine. indicates the highly hypothetic protein functions deduced from bioinformatic analysis only.

The great structural complexity encountered among sesquiterpenes implies that multiple cyclizations, shifts, and rearrangements of the parent cyclic intermediates may occur before stabilization to the final product, and in many instances several routes to the same sesquiterpene are feasible. Whether such reactions are concerted, take place sequentially on the enzyme surface, or involve discrete free intermediates is not yet generally known, and all three mechanistic alternatives, as well as multiple pathways, have been invoked to rationalize the same sesquiterpene structures. Because very few cell-free systems are available to examine these questions directly, and because of the difficulties associated with obtaining direct evidence of biosynthetic routes via in vivo tracer studies, hypothetic il pathways based mainly on chemical reasoning have been the rule (Roberts, 1972 Rucker, 1973 Anderson ef al., 1978). 

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