De novo synthesis

In most de novo procedures, the yield of the main compound is usually 100 mg 1 . Better yields are achieved when a substrate biochemically more immediate to the volatile product is used, or when an immediate precursor is included in the culture medium together with the crude substrate, thus obtaining processes that are closer to bioconversion procedures (see next paragraph). For example, the production of the peach-like aroma y-decalactone by Yarrowia lipolytica and various Candida species can exceed 10 g 1 if castor oil is included in the culture [25,26]. 

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The mode of action has been a subject for research for a number of years. While it was originally thought that maleic hydrazide replaced uracil in the RNA sequence, it has been deterrnined that the molecule may be a pyrimidine or purine analogue and therefore base-pair formation is possible with uracil and thymine and there exists the probabiHty of base-pair formation with adenine however, if maleic hydrazide occurs in an in vivo system as the diketo species, then there remains the possibiHty of base-pairing with guanine (50). Whatever the mechanism, it is apparent that the inhibitory effects are the result of a shutdown of the de novo synthesis of protein. 

The proposed mechanism by which chlorinated dioxins and furans form has shifted from one of incomplete destmction of the waste to one of low temperature, downstream formation on fly ash particles (33). Two mechanisms are proposed, a de novo synthesis, in which PCDD and PCDF are formed from organic carbon sources and Cl in the presence of metal catalysts, and a more direct synthesis from chlorinated organic precursors, again involving heterogeneous catalysis. Bench-scale tests suggest that the optimum temperature for PCDD and PCDF formation in the presence of fly ash is roughly 300°C. 

Thompson, E. M., Nafpakdds, B. G., and Tsuji, F. I. (1987). Induction of bioluminescence in the marine fish, Porichthys, by Vargula (crustacean) luciferin. Evidence for de novo synthesis or recycling of luciferin. Pho-tochem. Photobiol. 45 529-533. 

Terpenoid substances are of broad distribution and diverse function in insects. One set, elaborated by the mandibular glands of Acanthomyops claviger, acts both as a defensive secretion and as an alarm releaser. When fed Cu-labeled acetate or mevalonate, laboratory colonies of these ants produce radioactive citronellal and citral, providing unambiguous evidence for de novo synthesis of these terpenes by the ant. The incorporations of these precursors implicate the mevalonic acid pathway as the likely biosynthetic route. 

Inosine monophosphate dehydrogenase (EVDPDH) is a key enzyme of purine nucleotide biosynthesis. Purine synthesis in lymphocytes exclusively depends on the de novo synthesis, whereas other cells can generate purines via the so-called salvage pathway. Therefore, IMPDH inhibitors preferentially suppress DNA synthesis in activated lymphocytes. 

Type I allergic reactions are inappropriate immune responses to an allergen with preferential synthesis of immunoglobulin E (IgE), a special antibody class, which binds to mast cells and basophilic granulocytes via Fee receptors. Binding of the allergen to the cell-bound IgE initiates the rapid release of allergic mediators, most prominently histamine, and the de novo synthesis of arachidonic acid metabolites and cytokines, which are responsible for the clinical symptoms. 

The general approach has been followed for the de novo synthesis of a multitude of differently substituted, unsaturated [112,113] or regiospedfically labeled sugars [102,114]. Unusual branched-chain (42), (43)) and spiro-annulated sugars (45), (46)) have been synthesized from the corresponding aldehyde precursors... 

Hofner, R., Vazquez-Morena, L., Winter, K., Bohnert, H.J. Schmitt, J.M. (1987). Induction of Crassulacean acid metabolism in Mesembryanthemum crystallinum by high salinity mass increase and de novo synthesis of PEP-carboxylase. Plant Physiology, 83, 915-19. 

Several physiological changes induced by drought have been documented, including an increase in ABA levels, the closure of stomata and the increase in cellular osmolarity. The increase in ABA levels is probably due to the de novo synthesis of this hormone, and the process requires... 

Cyanobacteria, prokaryotic algae that perform oxygenic photosynthesis, respond to a decrease in ambient growth temperature by desaturating the fatty acids of membrane lipids to compensate for the decrease in the molecular motion of the membrane lipids at low temperatures. During low-temperature acclimation of cyanobacterial cells, the desaturation of fatty acids occurs without de novo synthesis of fatty acids [110, 111]. All known cyanobacterial desaturases are intrinsic membrane proteins that act on acyl-Hpid substrates. 

The source of long-chain fatty acids is either dietary lipid or de novo synthesis from acetyi-CoA derived from carbohydrate. Fatty acids may be oxidized to acetyl-CoA (P-oxidation) or esterifred with glycerol, forming triacylglycerol (fat) as the body s main fuel reserve. 

THE MAIN PATHWAY FOR DE NOVO SYNTHESIS OF FATTY ACIDS (LIPOGENESIS) OCCURS IN THE CYTOSOL... 

Conversion of purines, their ribonucleosides, and their deoxyribonucleosides to mononucleotides involves so-called salvage reactions that require far less energy than de novo synthesis. The more important mechanism involves phosphoribosylation by PRPP (structure II, Figure 34-2) of a free purine (Pu) to form a purine 5 -mononucleotide (Pu-RP). 

Kuzuhara S, H Sato, N Tsubouchi, Y Ohtsuka, E Kasai (2005) Effect of nitrogen-containing compounds on polychlorinated dibenzo-p-dioxin/dibenzofuran formation through de novo synthesis. Environ Sci Technol 39 795-799. 

Janke D (1987) Use of salicylate to estimate the threshold inducer level for de novo synthesis of the phenoldegrading enzymes in Pseudomonas putida strain H. J Basic Microbiol 27 83-89. 

Figure 13.8 De novo synthesis of 2-methyl hutanoyl CoA and 2-methyl propionyl CoA...

How could such difficulties be avoided Shapiro lists minerals which could have served either as the first replicators or as highly selective polymerases. He also considers a further possibility life may have begun as a metabolic network of reactions which involved monomers the replicators may have evolved in a later evolutionary phase. The misgivings mentioned, and the open questions referred to in earlier chapters, indicate that a de novo synthesis of RNA under the conditions present on the young Earth was almost impossible. Thus, models were and are being looked for which could bypass as many as possible of the problems referred to. 

Evidence for de novo synthesis of pheromone components was obtained by showing that labeled acetate and mevalonate were incorporated into ipsdienol by male Ips pini [103,104]. Similarly, labeled acetate and other labeled intermediates were shown to be incorporated into frontalin in a number of Dendroctonus species [105]. Possible precursors to frontalin include 6-methyl-6-hep-ten-2-one, which was incorporated into frontalin by D. ruffipennis [106]. The precursor 6-methyl-6-hepten-2-one also was shown to be converted to bre-vicomin in the bark beetle, Dendroctonus ponderosae [107]. In addition, the expression patterns of HMG-CoA reductase and HMG-CoA synthase are tightly correlated with frontalin production in Dendroctonus jeffreyi [108, 109]. A geranyl diphosphate synthase cDNA from I. pini was also isolated, functionally expressed, and modeled [110]. These data indicate that the de novo isoprenoid biosynthetic pathway is present in bark beetles. A variety of other monoterpene alcohols such as myrcenol, pityol, and sulcitol are probably synthesized through similar pathways [111]... 

In contrast to the Johnson s D —> A-ring construction approach, Brown devised an A —> D-ring construction approach [22]. Starting from Wieland-Miescher ketone (30), a common source of the A, B-rings in the de novo synthesis of steroids, the C-ring was introduced via hydrazone allylation, ozonolysis, aldol condensation, and olefin isomerization (31 > 32). The D-ring was assembled by a reductive alkylation... 

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