Volume 19 Issue 8, August 2023

Protein glycation has long-been considered a toxic consequence of carbohydrate metabolism. Yet recent evidence demonstrates tight regulation for these non-enzymatic post-translational modifications, pointing to a broader role in cell biology rather than simply serving as a biomarker for toxicity.

Bacterial biofilms are resilient multicellular communities with spatially complex localized interactions that remain largely uncharacterized. A new approach called RainbowSeq enables transcriptional profiling in biofilms with increased spatial resolution.

Identifying new proteoforms — structural variants of proteins — is frequently challenging, particularly on the proteome-wide scale. A new study leverages their differential thermal stabilities to identify proteoform functional groups by deep thermal proteome profiling.

Sodium bisulfite is widely used in methylation sequencing, yet it degrades DNA, and on its own, it does not discriminate methylated cytosine from its oxidized derivative, 5-hydroxymethylcytosine. A new bisulfite-free technique uses enzymatic modification of DNA for direct and accurate methylation mapping.

Modular polyketide synthases are multidomain megasynthases catalyzing polyketide chain elongation, modification and release. New work reveals a full ~360-kDa modular polyketide synthases with just one active domain, ketosynthase, catalyzing an amidation that releases the completed product (a reaction type typically catalyzed by dedicated thioesterases).

A study has now shown that copper ions can drive inflammation via a mitochondrial signaling pathway that regulates epigenetic states of immune cells. This pathway could offer a new route for treating inflammatory diseases.

Development of a novel spatial transcriptomics method, RAINBOW-seq, enables probing of the heterogeneity in a bacterial community, revealing rich coordination of metabolism in the E. coli biofilm to mediate collective fitness.

Systematically culturing combinations of auxotrophic yeast mutants leads to the identification of pairs that form obligatory cross-feeding relationships, some of which are stable over time and can divide metabolic labor for biotechnological applications.

Applying thermal proteome profiling to acute B cell childhood leukemia cell lines combined with deep peptide fractionation and a graph-based clustering algorithm allows inference of functional proteoform groups and their association with drug response.

Kim et al. used directed evolution methods to identify a high-fidelity SpCas9 variant, Sniper2L, which exhibits high general activity but maintains high specificity at a large number of target sites.

A chemically controlled Cas9 switch offers a simple, general approach to temporal control of Cas9 effectors, including transcriptional activators, base editors and a prime editor. Chemically controlled base editors revealed bystander editing kinetics.

Characterization of the conformation landscape of the bacterial ABC transporter CydDC reveals that this heterodimeric protein complex is a long-sought heme transporter essential for the functional maturation of bd-type cytochromes.

Wang et al. developed a bisulfite-free method termed DM-Seq that leverages an unnatural enzyme–substrate pair coupled with a DNA deaminase to sequence 5-methylcytosine at base resolution in sparse DNA samples, circumventing the limitations of chemical deamination methods.

The RXFP1 relaxin receptor is a critical mediator of physiological adaptation to pregnancy and an emerging drug target. RXFP1 activation was found to entail an unexpected mechanism of ectodomain disinhibition resulting in downstream signaling.

The structure, molecular and mechanistic details of the human α1,3-fucosyltransferase FUT9 provide insight into the synthesis of diverse and modified glycan-capping Lewis antigen structures by a conserved family of mammalian fucosyltransferases.

The medicinal plant Catharanthus roseus is a source of leading anticancer drugs. The monoterpene indole alkaloid (MIA) biosynthetic pathway in C. roseus has now been analyzed using a complementary, multi-omics, single-cell approach. This identified clusters of genes involved in MIA biosynthesis and cell-type-specific partitioning in the MIA biosynthetic pathway.