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IMPORTANCEIt remains unknown whether SARS-CoV-2 infection specifically increases the risk of serious obstetric morbidity.OBJECTIVE To evaluate the association of SARS-CoV-2 infection with serious maternal morbidity or mortality from common obstetric complications.
Bis-indolylquinones represent a class of fungal natural products that display antiretroviral, antidiabetes, or cytotoxic bioactivities. Recent advances in Aspergillus genomic mining efforts have led to the discovery of the tdiA-E-gene cluster, which is the first genetic locus dedicated to bis-indolylquinone biosynthesis. We have now genetically and biochemically characterized the enzymes TdiA (bis-indolylquinone synthetase) and TdiD (L-tryptophan:phenylpyruvate aminotransferase), which, together, confer biosynthetic abilities for didemethylasterriquinone D to Aspergillus nidulans. This compound is the universal intermediate for all bis-indolylquinones. In this biochemical study of a bis-indolylquinone synthetase and a fungal natural product transaminase, we present a one-pot chemoenzymatic protocol to generate didemethylasterriquinone D in vitro. As TdiA resembles a nonribosomal peptide synthetase, yet catalyzes carbon-carbon-bond formation, we discuss the implications for peptide synthetase chemistry.
Ralstonia solanacearum is a destructive crop plant pathogen and produces ralfuranone, i.e., a monophenyl-substituted furanone. Extensive feeding experiments with (13)C-labeled L-phenylalanine now proved that all carbon atoms of the heterocycle derive, after deamination, from this aromatic amino acid. A genetic locus was identified which encodes the aminotransferase RalD and the furanone synthetase RalA. The latter is a tridomain nonribosomal peptide synthetase (NRPS)-like enzyme which was characterized (1) biochemically by the ATP-pyrophosphate exchange assay, and (2) genetically through gene inactivation and transcriptional analysis in axenic culture and in planta. This is the first study to our knowledge on the biochemical and genetic basis of R. solanacearum secondary metabolism. It implies new chemistry for NRPSs, as RalA-mediated biosynthesis requires C-C-bond and subsequent C-O-bond formation to establish the furanone ring system.
Microbial natural products, among them a vast diversity of fungal origin, represent a major source for new drug candidates. Focusing on fungal metabolites, our review covers recent advances in the field of biotransformation, heterologous expression, in vivo production approaches, genomics, and the metabolism of unexplored fungal groups as options to generate and identify new compounds or optimize known ones.
Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood.
Die Anwendung der Metathese, besonders der Ringschlussmetathese (RCM) zur Bildung von Fünf‐ und Sechsringen, ist heute in der organischen Chemie weit verbreitet; dennoch gibt es überraschend wenige Beispiele für ihre Anwendung zur Synthese aromatischer Verbindungen. Deren Bedeutung in der medizinischen Chemie und der Naturstoffsynthese, verbunden mit der Wirksamkeit von RCM‐Katalysatoren und ihrer Toleranz gegenüber funktionellen Gruppen, gibt Anlass, die Anwendung der RCM in der Arensynthese zu untersuchen. Die Synthese von heterocyclischen und carbocyclischen Arenen unter Verwendung der RCM wird in einigen Publikationen als Schlüsselschritt beschrieben. Galt das gebildete Aren in vielen frühen Beispielen noch als unerwünschtes Abbauprodukt, so wurden in letzter Zeit gezielt Methoden zur Arensynthese über RCM entwickelt.
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