Control of secondary metabolism

The control of secondary metabolism is discussed earlier in this chapter. In summary, a number of factors have been identified which trigger and control secondary metabolism. Understanding these triggers can be useful during the design of the environmental conditions to be used to grow fungi. 

Bypassing Control of Secondary Metabolism. Since the production of secondary metabolites is affected by genetically determined mechanisms - derepression (induction), catabolite regulation, and feedback regulation - it is clear that mutation should have a major effect on the production of secondary metabolites. Indeed, the chief factor responsible for the 100- to 1000-fold increases in production of antibiotics ftom the... 

The ability of glyphosate to block phenylalanine synthesis, resulting in shikimate accumulation, makes this herbicide a useful tool for examining control of secondary metabolism. 

Luckner, Expression and control of secondary metabolism. In Ehoyclopaedia of Plant Physiology - Hew Series. Vol. 8 Secondary Plant Products. Springer Verlag. Berlin, in press. 

Luckner, M. Expression and control of secondary metabolism. In Encyclopedia of Plant Physiology, New Series, Vol. 8, Secondary Plant Products (E. A. Bell, B. V. Charlwood, eds.), pp. 23-63. Springer, Berlin-Heidelberg-New York 1980 Margna, U. Control at the level of substrate supply - an alternative in the regulation of phenyl-propanoid accumulation in plant cells. Phytochemistry 16, 419-426 (1977)... 

In the following sections some general principles are discussed, which show the interrelations between the control of secondary metabolism and other metabolic activities of the producer organisms. 

Herbicides are the biocides most likely to affect the metabolism of plants, including secondary metabolism [107]. The synthesis of hydroxyphenolics and anthocyanin in plants can be influenced by a variety of environmental and chemical stimuli. Some herbicides were found to raise the levels of these compounds in plants [108] whilst others had the opposite effect [109]. The products of secondary metabolism are controlled by enzymes, including PAL and chalcone isomerase (Cl), and several herbicides appear to intensify the activities of those enzymes involved in the accumulation of hydroxyphenolic compounds and anthocyanin biosynthesis in several plant species [109-111] whereas others depress this activity [112]. For example,... 

KLIEBENSTEIN, D.J., LAMBR1X, V.M., REICHELT, M., GERSHENZON, J., MITCHELL-OLDS, T., Gene duplication in the diversification of secondary metabolism Tandem 2-oxoglutarate-dependent dioxygenases control glucosinolate biosynthesis in Arabidopsis., Plant Cell, 2001,13,681-693. 

Alkaloid biosynthetic pathways are under strict regulation in plants. Until now, our limited knowledge of the fundamental mechanisms involved in the control of alkaloid metabolism has severely restricted our ability to harness the vast biotechnological potential of these important secondary pathways. For example, the use of plant cell cultures for the commercial production of pharmaceutical alkaloids has not become a reality despite decades of empirical research. The application of traditional and modem biochemical, molecular, and cellular techniques has revealed important clues about the reasons why C. rosens cultures accumulate tabersonine and catharanthine, but not vindoline or vinblastine, and why opium poppy cultures produce sanguinarine, but not codeine or morphine. The inability of dedifferentiated cells to accumulate certain metabolites was interpreted as evidence that the operation of many alkaloid pathways is tightly coupled to the development of specific tissues. Recent studies have shown that alkaloid pathways are regulated at multiple levels,... 

This latter more focussed approach involves the identification of genes encoding metabolic enzymes which will allow full control of a given pathway. Indeed, the engineering of medicinal plants for the production of valuable natural products has been attained [48,61,170]. However, the major barrier for the successful metabolic engineering of pathways is still the limited knowledge of secondary metabolism pathways. 

Higher plants have evolved an extraordinary variety of secondary metabolic pathways, the resulting products of which have been put to use by man providing pharmaceuticals for drug use, insecticides and various allelochemicals for pest control, and extracts for the flavor and fragrances industries. In spite of advances in synthetic organic chemistry, plants remain a major source of natural products, particularly in the specialty chemicals industry. Compounds, such as the insecticide derived from Azadiraohta indioa or the antitumor alkaloids vinblastine and vincristine found in periwinkle (Catharanthus roseus) (1 ), have complicated structures which preclude at the present time the development of an economical chemical synthesis (Figure 1). In the case of... 

Thus, the chapters presented here are a microcosm of what the recent completion, or near completion, of various genome projects are enabling biochemists to understand not only about control and regulation of secondary metabolism, and how various pathways relate to each other, but also about its relation to primary metabolism. A major paradigm shift is occurring in the way we need to view secondary metabolism in the future. It is also clear that model systems, such as the ones discussed in the symposium, are providing new information and insight almost faster than we can process it ... 

Martin JF. Molecular mechanisms for the control by phosphate of the biosynthesis of antibU otics and other secondary metabolites. Shapiro S, ed. Regulation of Secondary Metabolism in Actinomyceies. Boca Raton. Florida CRC Press, 1989 213-237. 

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