Trehalose is a nonreducing disaccharide that plays a major role in many organisms, most notably in survival and stress responses. In Mycobacterium tuberculosis, it plays a central role as the carbohydrate core of numerous immunogenic glycolipids including "cord factor" (trehalose 6,6'-dimycolate). The classical pathway for trehalose synthesis involves the condensation of UDP-glucose and glucose-6-phosphate to afford trehalose-6-phosphate, catalyzed by the retaining glycosyltransferase OtsA. The configurations of two anomeric positions are set simultaneously, resulting in the formation of a double glycoside. The three-dimensional structure of the Escherichia coli OtsA, in complex with both UDP and glucose-6-phosphate, reveals the active site at the interface of two beta/alpha/beta domains. The overall structure and the intimate details of the catalytic machinery reveal a striking similarity to glycogen phosphorylase, indicating a strong evolutionary link and suggesting a common catalytic mechanism.

To cause rice blast disease, the fungus Magnaporthe oryzae breaches the tough outer cuticle of the rice leaf by using specialized infection structures called appressoria. These cells allow the fungus to invade the host plant and proliferate rapidly within leaf tissue. Here, we show that a unique NADPH-dependent genetic switch regulates plant infection in response to the changing nutritional and redox conditions encountered by the pathogen. The biosynthetic enzyme trehalose-6-phosphate synthase (Tps1) integrates control of glucose-6-phosphate metabolism and nitrogen source utilization by regulating the oxidative pentose phosphate pathway, the generation of NADPH, and the activity of nitrate reductase. We report that Tps1 directly binds to NADPH and, thereby, regulates a set of related transcriptional corepressors, comprising three proteins, Nmr1, Nmr2, and Nmr3, which can each bind NADP. Targeted deletion of any of the Nmr-encoding genes partially suppresses the nonpathogenic phenotype of a Δtps1 mutant. Tps1-dependent Nmr corepressors control the expression of a set of virulence-associated genes that are derepressed during appressorium-mediated plant infection. When considered together, these results suggest that initiation of rice blast disease by M. oryzae requires a regulatory mechanism involving an NADPH sensor protein, Tps1, a set of NADP-dependent transcriptional corepressors, and the nonconsuming interconversion of NADPH and NADP acting as signal transducer.fungal pathogenicity | ascomycete | cofactor R ice blast disease represents a significant constraint on worldwide rice production, resulting in severe epidemics and overall global yield losses of 10-30% each year (1). Rice constitutes 23% of the calories consumed annually by the global human population, so understanding and controlling rice blast disease could play an important role in ensuring global food security in the future (2). To infect rice plants, the blast fungus Magnaporthe oryzae produces specialized infection cells called appressoria, which rupture the leaf cuticle and allow fungal hyphae to invade and colonize the host. The fungus is able to proliferate rapidly within rice cells, deriving nutrition from living tissue while evading or suppressing plant defenses (1). Understanding the regulatory mechanisms that allow the fungus to undergo these developmental transitions and to grow so effectively within its host may provide new means to control rice blast disease.In this study, we set out to investigate the gene regulatory mechanisms that condition the ability of M. oryzae to respond to the nutrient status of its environment during plant infection-moving from the nutrient-free conditions of the rice leaf surface to the relatively nutrient-rich interior of the leaf. Previously, we observed a pivotal role for the biosynthetic enzyme trehalose-6-phosphate synthase (Tps1) in the regulation of carbon and nitrogen metabolism in M. oryzae (3, 4). Tps1 is required for production of the nonreducing disaccharide trehalose from glucose-6-phosphate (G6...

Trehalose fulfils a wide variety of functions in cells, acting as a stress protectant, storage carbohydrate and compatible solute. Recent evidence, however, indicates that trehalose metabolism may exert important regulatory roles in the development of multicellular eukaryotes. Here, we show that in the plant pathogenic fungus Magnaporthe grisea trehalose-6-phosphate (T6P) synthase (Tps1) is responsible for regulating the pentose phosphate pathway, intracellular levels of NADPH and fungal virulence. Tps1 integrates glucose-6-phosphate (G6P) metabolism with nitrogen source utilisation, and thereby regulates the activity of nitrate reductase. Activity of Tps1 requires an associated regulator protein Tps3, which is also necessary for pathogenicity. Tps1 controls expression of the nitrogen metabolite repressor gene, NMR1, and is required for expression of virulence-associated genes. Functional analysis of Tps1 indicates that its regulatory functions are associated with binding of G6P, but independent of Tps1 catalytic activity. Taken together, these results demonstrate that Tps1 is a central regulator for integration of carbon and nitrogen metabolism, and plays a pivotal role in the establishment of plant disease.

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Strong inhibitions: The inhibition of trehalases, enzymes which hydrolyze the disaccharide trehalose, is a target for novel antibiotic insecticides. The structures (see picture; C black, N blue, O red, S yellow) of a trehalase in complex with validoxylamine A (yellow) and 1‐thiatetrazolin (blue) reveal that the inhibitors tightly bind to the enzyme through hydrogen bonds.

Such information as is available concerning nutrition within the phylum Rhynchocoela is largely restricted to reports on the food and feeding mechanisms of relatively few species. The group, which is predominantly free living in habit, is generally regarded as carnivorous or scavenging, and potential food is detected SEVEN SPECIES OF RHYNCHOCOELAN WORMS." The Biological bulletin 136, 405-433.

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