Aromatic side-chain crosslinking in RiPP biosynthesis
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Anthropogenic organic aerosol in Europe produced mainly through second-generation oxidation
Exposure to anthropogenic atmospheric aerosol is a major health issue, causing several million deaths per year worldwide. The oxidation of aromatic hydrocarbons from traffic and wood combustion is an important anthropogenic source of low-volatility species in secondary organic aerosol, especially in heavily polluted environments. It is not yet established whether the formation of anthropogenic secondary organic aerosol involves mainly rapid autoxidation, slower sequential oxidation steps or a combination of the two. Here we reproduced a typical urban haze in the ‘Cosmics Leaving Outdoor Droplets’ chamber at the European Organization for Nuclear Research and observed the dynamics of aromatic oxidation products during secondary organic aerosol growth on a molecular level to determine mechanisms underlying their production and removal. We demonstrate that sequential oxidation is required for substantial secondary organic aerosol formation. Second-generation oxidation decreases the products’ saturation vapour pressure by several orders of magnitude and increases the aromatic secondary organic aerosol yields from a few percent to a few tens of percent at typical atmospheric concentrations. Through regional modelling, we show that more than 70% of the exposure to anthropogenic organic aerosol in Europe arises from second-generation oxidation.
KorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid
Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB–KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.5 kb away. We resolved the tripartite crystal structure of a KorB–KorA–DNA co-complex, revealing that KorA latches KorB into a closed clamp state. DNA-bound KorA thus stimulates repression by stalling KorB sliding at target promoters to occlude RNA polymerase holoenzymes. Together, our findings explain the mechanistic basis for KorB role switching from a DNA-sliding clamp to a co-repressor and provide an alternative mechanism for long-range regulation of gene expression in bacteria.
Global food retail environments are increasingly dominated by large chains and linked to the rising prevalence of obesity
Retail food environments influence food purchasing and dietary patterns. A global analysis of the food retail landscape allowing comparisons across geographical regions is therefore needed to tackle diet-related non-communicable diseases. Here we examine trends in retail food environments from 2009 to 2023 across 97 countries, exploring associations with changes in obesity prevalence. Increases were observed in the density of chain outlets, grocery sales from chain retailers, unhealthy food sales per capita and digital grocery sales; non-chain outlet density and the ratio of non-chain to chain outlets declined over time. South Asia and low- and middle-income countries overall experienced the most rapid transformation. Changes in retail environments and the prevalence of obesity were found to be positively correlated. As retail environments become increasingly digital and dominated by large chains, important implications for diets and health should be expected, particularly in lower-income countries.
A glycan foldamer that uses carbohydrate–aromatic interactions to perform catalysis
In nature, the ability to catalyse reactions is primarily associated with proteins and ribozymes. Inspired by these systems, peptide-based catalysts have been designed to accelerate chemical reactions and/or ensure regio- and stereoselective transformations. We wondered whether other biomolecules (such as glycans) could be designed to perform catalytic functions, expanding the portfolio of synthetic functional oligomers. Here we report a glycan foldamer inspired by the natural Sialyl Lewis X antigen that acts as catalyst in a chemical reaction. This glycan-based catalyst benefits from structural rigidity and modular adaptability, incorporating a substrate-recognition motif alongside a catalytic active site. Leveraging the inherent ability of carbohydrates to engage in CH–π interactions with aromatic substrates, we demonstrate the recruitment and functionalization of a tryptophan via a Pictet–Spengler transformation. Our modular glycan catalyst accelerates the reaction kinetics, enabling the modification of tryptophan-containing peptides in aqueous environments. Our findings pave the way for the development of glycan-based catalysts and suggest the possibility of catalytic capabilities of glycans in biological contexts.
Rapid and sensitive protein complex alignment with Foldseek-Multimer
Advances in computational structure prediction will vastly augment the hundreds of thousands of currently available protein complex structures. Translating these into discoveries requires aligning them, which is computationally prohibitive. Foldseek-Multimer computes complex alignments from compatible chain-to-chain alignments, identified by efficiently clustering their superposition vectors. Foldseek-Multimer is 3–4 orders of magnitudes faster than the gold standard, while producing comparable alignments; this allows it to compare billions of complex pairs in 11 h. Foldseek-Multimer is open-source software available at GitHub via https://github.com/steineggerlab/foldseek/, https://search.foldseek.com/search/ and the BFMD database.
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