Secondary products formation

An excess of phosgene is used during the initial reaction of amine and phosgene to retard the formation of substituted ureas. Ureas are undesirable because they serve as a source for secondary product formation which adversely affects isocyanate stabiUty and performance. By-products, such as biurets (23) and triurets (24), are formed via the reaction of the labile hydrogens of the urea with excess isocyanate. Isocyanurates (25, R = phenyl, toluyl) may subsequendy be formed from the urea oligomers via ring closure. 

In this description we have made a clear distinction between growth and secondary product synthesis. You should, however, realise that the distinction is not quite so sharp in practice. Thus we might expect some, albeit a small amount, of secondary product formation in file trophophase and some growth of new cells replacing dead ones in the idiophase. Nevertheless, the separation of the process into two phases enables the optimisation of conditions for growth in one phase and the imposition of conditions which maximise production of antibiotic in the other. 

Secondary product formation Is also expected to result from the reaction of OH with the nltramlne, but the mechanism and products formed In this case Is more uncertain. 

Funk, C., Giigler, K. and Brodelius, P. E. 1987. Increased secondary product formation in plant cell suspension cultures after treatment with a yeast carbohydrate preparation (elicitor). Phytochemistry, 26 401 05. 

Hamill, J. D., Parr, A. J., Robins, R. J. and Rhodes, M. J. C. 1986. Secondary product formation by cultures of Beta vulgaris and Nicotiana rustica transformed with Agrobacterium rhizogenes. Plant Cell Reports, 5 111-114. 

Oxidation of Anionic Polymers In the Solid State The ability of the macroradical and of the macroions to diffuse In the mixture, and to interreact Is responsible for the secondary products formation coupling reaction and alcoholate synthesis. To prevent the diffusion phenomenon, we have carried out the deactivation In the solid state. The living polymers have been prepared In benzene, with or without a solvating agent (THF or TMEDA) and the solution has been freeze dried before the oxygen introduction. The experimental results are collected in Table VII. 

Logemann E, Tavernaro A, Schulz W, Somssich IE, Hahlbrock K. 2000. UV light selectively coinduces supply pathways from primary metabolism and flavonoid secondary product formation in parsley. Proc Nat Acad Sci USA 97 1903-1907. 

Brown, E.G. and Turan, Y. (1995) Pyrimidine metabolism and secondary product formation biogenesis of albizziine, 4-hydroxyhomoarginine and 2,3-diaminopropanoic acid. Phytochemistry, 40, 763-71. 

As with polystyrene sulfonic resins, Nafion-based acid catalysts are highly efficient for hydration and dehydration processes and, in general, for condensation reactions that occur with the formation of water or similar secondary products. Formation of ethers has been studied for various alcohols [109-111]. Dehydration of 1,4- and 1,5-diols at 135 °C affords the corresponding cyclic ethers such as 20 in excellent yields (Scheme 10.7), while 1,3-diols experience different transformations depending on their structure [112]. The dehydration of 1,2-diols mainly proceeds via the pinacol rearrangement. Further condensation of the initially formed carbonyl compound and unreacted diol affords 1,3-dioxolanes [113]. The catalyst could be efficiently reused following a reactivation protocol. Formation of aryl ethers is also possible, and the synthesis of dibenzofurans 21 (X = O) from 2,2 -dihydroxybiphenyls has been reported (Scheme 10.7) [114]. The related reaction... 

Secondary product formation is a form of differentiation, induction of the required type of differentiation does lead to secondary product formation, e.g. phytoalexins will readily be formed upon stress conditions (additions of fungal elicitors) and compounds usually found in the roots will also be found in root cultures or hairy-root (cells transformed with Agrobacterium rhizogenes) cultures. In Table 4 some examples are summarized of the influence of differentiation on secondary metabolite production. 

In order to study the integration of secondary product formation into sporulation, different methods have been used. By the use of whole cell- and cell free-systems it has been demonstrated that the production of secondary metabolites occurs at different stages in growth. Furthermore, experiments with mutants and inhibitors of gene expression indicate that the formation of some secondary products, among which are sulpholactic acid, dipicolinic acid, brown pigments and peptide antibiotics, is closely linked to the sporulation process (Ref. 14, 19). 

A relatively large part of the producer organism genome may be involved in secondary product formation. 

The beginning of secondary product formation is often directly coupled with the synthesis of the corresponding enzymes. One example is the biosynthesis of flavonoids in cell cultures of Petroselinum hortense (Fig. 7). Here the regulatory mechanisms were extensively investigated with phenylalanine ammonia-lyase (PAL) (D 22.2.1) and chalcone synthase (D 22.3.3), the key enzymes of the biosynthetic chain. Experiments with inhibitors of transcription and translation showed that the increase of enzyme activity depends on RNA and protein biosynthesis. Labeling experiments demonstrated that it is caused by an accelerated rate of enzyme synthesis. 

A Determination in vitro of an activity increase of enzymes of secondary metabolism before or at the beginning of the phase of secondary product formation. 

C Isotope-labeling of enzymes catalyzing secondary product formation to demonstrate their de novo formation at certain developmental phases of the producer organism. 

It is, however, not the only mechanism regulating enzyme amount. Experiments with actinomycin D (D 8.4.1), an inhibitor of transcription, revealed a considerable gap between the onset of transcription and the actual beginning of secondary product formation in dipicolinic acid biosynthesis (D 18) during bacterial sporulation. This suggests control of enzyme synthesis on the transcriptional and on one of the posttranscriptional levels. The bacteria probably have stable mRNA species whose translation offers a second level of control of the overall process. 

The phase-dependent expression of secondary metabolism designated in A 4.1 as one of the most important features in the control of secondary product formation is caused by the integration of secondary metabolism in the programs of differentiation and development. These programs, which are characteristic of all living cells... 

Suppression of secondary product formation by excess nutrients, especially by glucose and other easily degradable carbon sources, but also by nitrogen-containing compounds and phosphate, is a general phenomenon in microbial cultures. 

Suppression by excess nutrients has been found in the biosynthesis of polyketides (D 3.3), of gibberellins (D 6.3), of certain antibiotics, e.g., streptomycin (D 1.3), neomycin C (D 1.3), actinomycins (D 8.4.1), chloramphenicol (D 8.2), bacitracin A (D 23), enniatin B (D 23), cephalosporins (D 23.3), and penicillins (D 23.3), of alkaloids, e.g., benzodiazepines (D 8.4.2), and ergolines (D 21.2) etc. Usually the suppression of secondary product formation is accompanied by the suppression of other characteristics of cell specialization (such as conidiospore formation in Peni-cillium cyclopium), indicating a general influence of nutrient supply on cell specialization. 

Usually the response of the target cells depends on their state of differentiation (competence). Since secondary metabolism is integrated into differentiation programs, the phase during which secondary metabolism may be influenced is not necessarily linked directly to the stage of secondary product formation. 

The following microbial signal substances, for instance, are active only if added at the beginning of the growth phase, i.e., at a developmental stage before secondary product formation is actually expressed (determination phase) ... 

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