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Engineering alkaloids in plants. Runguphan and O'Connor (p 151) transform an engineered alkaloid biosynthetic gene into Catharanthus roseus to metabolically reprogram the plant's alkaloid pathway. When transgenic plant cultures were fed modified substrates, the plants produced unnatural alkaloid compounds (see also News and Views by Ryan and Moore on p 140). The cover shows a mosaic of C. roseus plants and tissue culture representing the various stages of the genetic engineering and plant transformation processes. Cover art by Erin Boyle based on images provided by Weerawat Runguphan.
Providers and users of chemical libraries must adopt quality and reporting standards to advance the impact of small-molecule high-throughput screening.
Receptor heteromers constitute a new area of research that is reshaping our thinking about biochemistry, cell biology, pharmacology and drug discovery. In this commentary, we recommend clear definitions that should facilitate both information exchange and research on this growing class of transmembrane signal transduction units and their complex properties. We also consider research questions underlying the proposed nomenclature, with recommendations for receptor heteromer identification in native tissues and their use as targets for drug development.
Biological membranes are dynamic frontiers whose molecules must delicately balance the needs for compartmentalization and communication, and the gap between the vital significance of transport and signaling through membranes and our poor understanding of the precise functionality of these processes is daunting. However, a recent conference highlighted promising progress in the field, particularly made possible by the increasing structural knowledge about membrane proteins.
Engineered biosynthesis of modified natural products normally uses microbes as biochemical factories. Now, chemical biologists are taking advantage of the largely untapped biochemical potential of plants.
Exposure to zinc can cause pain and inflammation and can be harmful to human health. New evidence suggests that activation of the irritant receptor, TRPA1, which is expressed on pain-sensing neurons, may be responsible for some of these symptoms of zinc toxicity.
Under iron-depleted conditions, bacteria produce siderophores that bind iron and are then actively taken up by the cell. New structural and biochemical insights are reported for the synthetic pathway of achromobactin, a siderophore from the plant pathogen Pectobacterium chrysanthemi.
Inhibition of growth stimulatory pathways has emerged as a major focus of targeted cancer drug development. New insights regarding potent, transient inhibition of cell signaling may challenge the dogma of medicinal chemistry and clinical trial design.
Newly synthesized secretory and membrane proteins contain cleavable signal sequences at the N terminus that allow for cotranslational protein targeting by interaction with the signal recognition particle (SRP). New results now suggest that signal sequences enable the conserved SRP RNA to accelerate complex formation with the SRP receptor.