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The native stress-tolerant phenotypes of various non-conventional microbes have the potential to enable more efficient bioprocessing for chemical production, addressing certain design challenges encountered when using model production hosts.
This Perspective focuses on the chemical basis of ferroptotic cell death, discussing the prominent role of spontaneous chemical reactions, how they depend on enzyme-catalyzed processes and how to exploit this interplay for therapeutic benefit.
This Perspective summarizes recent discoveries that have laid the foundation for targeted degradation therapeutics and discusses the current state of understanding and consideration involved in developing these protein degraders.
Synthetic biology is enabling functional metagenomics by providing genetic circuits to identify new pathways that, in turn, facilitate design of new biosensors and synthetic systems.
This Perspective explores the diversity, mechanisms and practical aspects of natural and engineered CRISPR-associated nucleases for genome engineering applications.
Synthetic biology offers innovative approaches for engineering biological systems, but also supports the development of biocontainment strategies that ensure the safe application of genetically modified organisms.
Through molecular grafting, cyclic disulfide-rich peptides can be used as scaffolds to improve the stability, rigidity, and cellular uptake of bioactive peptides, although a number of factors should be considered when designing such grafted peptides.
Targeting the host during antibiotic discovery efforts is a viable strategy, and the approach has benefited from phenotypic screening of model organisms such as worms, zebrafish, and mice.
Structure-based computational methods have contributed to recent successes in the development of small molecules to study GPCR function and to act as therapeutics, including the identification of new ligands for orphan GPCRs, allosteric regulators, and biased ligands.
Allosteric modulation and biased agonism at GPCRs could be manifestations of the same underlying 'conformational selection' mechanism, and these can be harmonized by considering the influence of ligand–receptor residence time and kinetic context.
The organelles and subcellular compartments of yeast provide distinct environments and physical separation from the cytosol, enabling opportunities to target biosynthetic pathways to these compartments and enhance production of desirable compounds.
A variety of chemical and enzymatic techniques, each with their own considerations for use, have been developed for the site-selective bioconjugation of desirable moieties to proteins via the unique handle of the N terminus.
Recent advances in metabolic engineering provide possible new approaches for the production of advanced intermediates as tractable semisynthetic starting materials for alkaloid-derived pharmaceuticals and potential new drugs.
This perspective discusses recent progress in the development of pharmacological tools that initiate mitophagy and spare mitochondrial function and focuses on promising approaches to identify improved reagents.
A Perspective focused on post-translational modifications of histone proteins and their selective recognition by epigenetic 'readers' highlights the importance of structural insights in understanding these key interactions in gene expression regulation.
Bioorthogonal chemistry approaches have traditionally focused on selective ligation reactions between compatible reactive groups. This Perspective highlights progress in developing bioorthogonal cleavage reactions for diverse applications in chemical biology.