Ronald Bentley

Bio: Ronald Bentley is an academic researcher. The author has contributed to research in topics: Shikimate pathway. The author has an hindex of 1, co-authored 1 publications receiving 635 citations.

The shikimate pathway.

Abstract: The shikimate pathway links metabolism of carbohydrates to biosynthesis of aromatic compounds. In a sequence of seven metabolic steps, phosphoenolpyruvate and erythrose 4-phosphate are converted to chorismate, the precursor of the aromatic amino acids and many aromatic secondary metabolites. All pathway intermediates can also be considered branch point compounds that may serve as substrates for other metabolic pathways. The shikimate pathway is found only in microorganisms and plants, never in animals. All enzymes of this pathway have been obtained in pure form from prokaryotic and eukaryotic sources and their respective DNAs have been characterized from several organisms. The cDNAs of higher plants encode proteins with amino terminal signal sequences for plastid import, suggesting that plastids are the exclusive locale for chorismate biosynthesis. In microorganisms, the shikimate pathway is regulated by feedback inhibition and by repression of the first enzyme. In higher plants, no physiological feedback inhibitor has been identified, suggesting that pathway regulation may occur exclusively at the genetic level. This difference between microorganisms and plants is reflected in the unusually large variation in the primary structures of the respective first enzymes. Several of the pathway enzymes occur in isoenzymic forms whose expression varies with changing environmental conditions and, within the plant, from organ to organ. The penultimate enzyme of the pathway is the sole target for the herbicide glyphosate. Glyphosate-tolerant transgenic plants are at the core of novel weed control systems for several crop plants.

The shikimate pathway and aromatic amino acid biosynthesis in plants.

Abstract: L-tryptophan, L-phenylalanine, and L-tyrosine are aromatic amino acids (AAAs) that are used for the synthesis of proteins and that in plants also serve as precursors of numerous natural products, such as pigments, alkaloids, hormones, and cell wall components. All three AAAs are derived from the shikimate pathway, to which ≥30% of photosynthetically fixed carbon is directed in vascular plants. Because their biosynthetic pathways have been lost in animal lineages, the AAAs are essential components of the diets of humans, and the enzymes required for their synthesis have been targeted for the development of herbicides. This review highlights recent molecular identification of enzymes of the pathway and summarizes the pathway organization and the transcriptional/posttranscriptional regulation of the AAA biosynthetic network. It also identifies the current limited knowledge of the subcellular compartmentalization and the metabolite transport involved in the plant AAA pathways and discusses metabolic engineering efforts aimed at improving production of the AAA-derived plant natural products.

Mycosporine-Like Amino Acids and Related Gadusols: Biosynthesis, Accumulation, and UV-Protective Functions in Aquatic Organisms

Abstract: Organisms living in clear, shallow water are exposed to the damaging wavelengths of solar ultraviolet radiation (UVR) coincident with the longer wavelengths of photosynthetically available radiation (PAR) also necessary for vision. With the general exception of bacteria, taxonomically diverse marine and freshwater organisms have evolved the capacity to synthesize or accumulate UV-absorbing mycosporine-like amino acids (MAAs), presumably for protection against environmental UVR. This review highlights the evidence for this UV-protective role while also considering other attributed functions, including reproductive and osmotic regulation and vision. Probing the regulation and biosynthesis of MAAs provides insight to the physiological evolution and utility of UV protection and of biochemically associated antioxidant defenses.

The Shikimate Pathway: Early Steps in the Biosynthesis of Aromatic Compounds.

Abstract: The shikimate pathway was discovered as the biosynthetic route to the aromatic amino acids phenylalanine, tyrosine, and tryptophan through the classic studies of Bernhard Davis and David Sprinson and their collaborators. This pathway has been found only in microorganisms and plants. Phenylalanine and tryptophan are essential components of animal diets, and animals synthesize tyrosine in a single step from phenylalanine. Thus, with respect to plant specificity, the shikimate pathway is a bit more widespread than nitrogen fixation or photosynthesis but less ubiquitous than, for example, nitrogen assi milat ion . Bacteria spend >90% of their total metabolic energy on protein biosynthesis. Consequently, the bacterial shikimate pathway serves almost exclusively to synthesize the aromatic amino acids (Herrmann, 1983; Pittard, 1987). In contrast, higher plants use these amino acids not only as protein building blocks but also, and in even greater quantities, as precursors for a large number of secondary metabolites, among them plant pigments, compounds to defend against insects and other herbivores (see Dixon and Paiva, 1995, this issue), UV light protectants, and, most importantly, lignin (Bentley, 1990; Singh et al., 1991; see Whetten and Sederoff, 1995, this issue). Under normal growth conditions, 20% of the carbon fixed by plants flows through the shikimate pathway (Haslam, 1993). Globally, this amounts to ~7 x 1015 kg each year, most of it used for the synthesis of the various secondary metabolites. And the variation in shikimate pathway-derived secondary metabolites is very extensive among plant species. The secondary metabolite makeup of a plant could be used for species classification. Different plants not only synthesize different aromatic secondary metabolites but also synthesize varying amounts of them at specific times and in specific subcellular compartments. One would expect that regulation of the differential biosynthesis of sometimes very complex molecular structures might involve regulation of the supply of the precursors influencing the rate-limiting step for carbon flow through the shikimate pathway. Recent data on transgenic potatoes give some indication that this is indeed the case (Jones et al., 1995). This review gives a short overview of the shikimate pathway and briefly introduces the seven enzymes that catalyze the sequential steps of the pathway. This is followed by a discussion of some enzymes of quinate metabolism, which use shikimate pathway intermediates as substrates, thus forming branches off the main trunk. I end by discussing some regulatory features of severa1 of the enzymes.

Interaction of the herbicide glyphosate with its target enzyme 5-enolpyruvylshikimate 3-phosphate synthase in atomic detail

Abstract: Biosynthesis of aromatic amino acids in plants, many bacteria, and microbes relies on the enzyme 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase, a prime target for drugs and herbicides. We have identified the interaction of EPSP synthase with one of its two substrates (shikimate 3-phosphate) and with the widely used herbicide glyphosate by x-ray crystallography. The two-domain enzyme closes on ligand binding, thereby forming the active site in the interdomain cleft. Glyphosate appears to occupy the binding site of the second substrate of EPSP synthase (phosphoenol pyruvate), mimicking an intermediate state of the ternary enzyme⋅substrates complex. The elucidation of the active site of EPSP synthase and especially of the binding pattern of glyphosate provides a valuable roadmap for engineering new herbicides and herbicide-resistant crops, as well as new antibiotic and antiparasitic drugs.