Myceliophthora thermophila M77 utilizes hydrolytic and oxidative mechanisms to deconstruct biomass

Biomass is abundant, renewable and useful for biofuel production as well as chemical priming for plastics and composites. Deconstruction of biomass by enzymes is perceived as recalcitrant while an inclusive breakdown mechanism remains to be discovered. Fungi such as Myceliophthora thermophila M77 appear to decompose natural biomass sources quite well. This work reports on this fungus fermentation property while producing cellulolytic enzymes using natural biomass substrates. Little hydrolytic activity was detected, insufficient to explain the large amount of biomass depleted in the process. Furthermore, this work makes a comprehensive account of extracellular proteins and describes how secretomes redirect their qualitative protein content based on the nature and chemistry of the nutritional source. Fungus grown on purified cellulose or on natural biomass produced secretomes constituted by: cellobiohydrolases, cellobiose dehydrogenase, B-1,3 glucanase, B-glucosidases, aldose epimerase, glyoxal oxidase, GH74 xyloglucanase, galactosidase, aldolactonase and polysaccharide monooxygenases. Fungus grown on a mixture of purified hemicellulose fractions (xylans, arabinans and arabinoxylans) produced many enzymes, some of which are listed here: xylosidase, mixed B-1,3(4) glucanase, B-1,3 glucanases, B-glucosidases, B-mannosidase, B-glucosidases, galactosidase, chitinases, polysaccharide lyase, endo B-1,6 galactanase and aldose epimerase. Secretomes produced on natural biomass displayed a comprehensive set of enzymes involved in hydrolysis and oxidation of cellulose, hemicellulose-pectin and lignin. The participation of oxidation reactions coupled to lignin decomposition in the breakdown of natural biomass may explain the discrepancy observed for cellulose decomposition in relation to natural biomass fermentation experiments.Peer reviewedMicrobiology and Molecular GeneticsBiochemistry and Microbiolog

A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo.

The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase (PfTyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidine ribose sulfamate, ML901, as a potent reaction hijacking inhibitor of PfTyrRS. Here we examined the stage specificity of action of ML901, showing very good activity against the schizont stage, but lower trophozoite stage activity. We explored a series of ML901 analogues and identified ML471, which exhibits improved potency against trophozoites and enhanced selectivity against a human cell line. Additionally, it has no inhibitory activity against human ubiquitin-activating enzyme (UAE) in vitro. ML471 exhibits low nanomolar activity against asexual blood stage P. falciparum and potent activity against liver stage parasites, gametocytes and transmissible gametes. It is fast-acting and exhibits a long in vivo half-life. ML471 is well-tolerated and shows single dose oral efficacy in the SCID mouse model of P. falciparum malaria. We confirm that ML471 is a reaction hijacking inhibitor that is converted into a tight binding Tyr-ML471 conjugate by the PfTyrRS enzyme. A crystal structure of the PfTyrRS/ Tyr-ML471 complex offers insights into improved potency, while molecular docking into UAE provides a rationale for improved selectivity

A new Eocaiman (Alligatoridae, Crocodylia) from the Itaboraí Basin, Paleogene of Rio de Janeiro, Brazil

A new small species of Eocaiman is described on the basis of three anterior left mandibular rami and one isolated tooth. The specimens came from the middle-upper Paleocene Itabora ́ı Basin (Rio de Janeiro State, Brazil; Itaboraian South American Land Mammal Age). The new taxon differs from the other two Eocaiman species, such as its small size, likely participation of the splenial in the mandibular symphysis, a reduced angle between the longitudinal axis of the symphysis and the mandibular ramus, and enlarged ninth and tenth dentary teeth (in addition to the large first and fourth dentary teeth). The participation of the splenial in the mandibular symphysis is a unique character among caimanines (with the only possible exception being Tsoabichi greenriverensis). The new taxon provides new information on the taxonomic and anatomical diversity of the genus Eocaiman, a taxon of prime importance to understand the evolutionary origins of caimans given its position as the basalmost member of Caimaninae. Furthermore, the new taxon has a relatively small body size in comparison with other species of Eocaiman, a case paralleled by other Itaboraian reptilian groups (e.g. snakes), suggesting that this ecosystem provides critical data to test the relationship between reptilian body size and climate.Fil: Pinheiro, André E. P.. Universidade Federal do Rio de Janeiro. Departamento de Geologia. Laboratório de Macrofósseis; BrasilFil: Fortier, Daniel C.. Universidade Federal do Rio Grande do Sul; Brasil. Universidade Federal de Minas Gerais. Intituto de Geociências; BrasilFil: Pol, Diego. Museo Paleontológico Egidio Feruglio; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Campos, Diógenes A.. Museu de Ciências da Terra. Departamento Nacional de Produção Mineral; BrasilFil: Bergqvist, Lílian P.. Universidade Federal do Rio de Janeiro. Departamento de Geologia. Laboratório de Macrofósseis; Brasi