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Assembly of the mycobacterial cell envelope layers, including peptidoglycan (PG) and the mycomembrane (MM), is synchronous during elongation, when a mobile fraction of the MM diffuses into the septum after thinning of the diffusion barrier formed by PG.
Discovery and exploitation of inherent reaction features of chlorofluoroacetamide (CFA) as a warhead such as low off-target activity and reversible reactivity with cysteine enable specific covalent inhibition of targeted kinases.
A cell-based phenotypic screen identifying inhibitors of Notch signaling led to the discovery of NVS-ZP7-4, which blocks the activity of the zinc transporter SLC39a7 (ZIP7) and induces cell death through an ER stress mechanism.
Screening with a small-molecule reactive-oxygen-species generator identifies the serine hydrolase enzyme ABHD12 as a lipase for the proapoptotic oxidized phoshatidylserine (ox-PS) lipids, which trigger production of proinflammatory cytokines.
The reconstitution of gentamicin B biosynthesis reveals the existence of multiple new intermediates and branching pathways and enables the identification of factors that contribute to the low levels of the natural product in the native producer.
Live-cell imaging and virus trafficking studies show that the host innate immune receptor IFITM3 localizes with endocytic vesicles that fuse with incoming viruses to ultimately enhance their traffic to lysosomes.
A combination of elicitor screening to induce expression of silent biosynthetic gene clusters with imaging mass spectrometry to visualize the resulting metabolome enables the discovery of nine cryptic natural products.