Volume 19 Issue 12, December 2023

Lysosomal hyperacidification is regarded as a hallmark of autophagy. A new pH nanosensor that detects shifts in near-infrared emission bands is used to quantify cellular and intratumoral lysosomal pH.

Medicinal drugs can cross-react with gut bacterial proteins, but the identification of these off-target interactions is difficult. Multi-omic approaches enabled the discovery of a bacterial peptidase that is inhibited by diabetic drugs and unexpectedly influences bacterial fitness within complex microbial communities via a non-proteolytic mechanism.

Newly developed synthetic antibodies offer the means to be used as high-affinity, conformation-specific probes to capture dynamic repertoires of neddylated cullin–RING E3 ligase complexes. This allows nonenzymatic profiling of the diverse signaling networks that are based on these active complexes.

Terpenoids bearing carbon skeletons derived from nonisoprene units are rare and considered noncanonical. Now, a genome-mining study has uncovered previously unknown noncanonical C₁₆ terpenes and their biosynthetic pathways from bacteria. The findings suggest that noncanonical terpenoids are diverse and widespread in nature.

We designed FAK-SPARK, a fluorescent reporter of focal adhesion kinase (FAK) activity based on phase separation. FAK-SPARK revealed polarized FAK activity within single focal adhesions in the leading edges of migrating cells. By combining FAK-SPARK with DNA tension probes, we showed that FAK activity is proportional to the tension strength.

We identified a comprehensive targetome for glycolytic metabolites in cancer cells using a novel target discovery approach — target responsive accessibility profiling (TRAP). The targetome revealed diverse regulatory modalities for glycolytic metabolites that include engaging with metabolic enzymes, influencing transcriptional outputs and modulating post-translational modification levels, thereby elucidating how glycolytic metabolites function as signaling molecules.

A carbon nanotube-based sensor was developed to monitor endolysosomal acidification events in live cells and in vivo. The technology enables a spatiotemporal measurement of endolysosomal pH and real-time tracking of the dynamics of autophagy in tumors.

Engineering of a focal adhesion kinase (FAK) reporter that visualizes endogenous FAK activity with dynamic spatiotemporal resolution in living cells and vertebrates reveals tension-induced polarized FAK activity in single focal adhesions during cell migration.

Bioinformatic and chemoproteomic approaches resulted in the identification of a homolog of human dipeptidyl peptidase 4 in the gut bacterium Bacteroides thetaiotaomicron that regulates envelope integrity and community fitness.

A chemoproteomic approach is developed that examines changes in ligand binding-induced accessibility by globally labeling reactive proteinaceous lysines, revealing the cellular targets of glycolytic intermediates.

Enolase 1 (ENO1) is a critical glycolytic enzyme that plays essential roles in pathological activities. Here, Sun, Suo, Zhang, Shen et al. reveal the nonmetabolic function of ENO1 in liver cancer, where ENO1 promotes YAP1 mRNA translation to activate arachidonic acid metabolism thus promoting cancer growth.

Tian et al. developed a bacterial orthogonal DNA replication system by harnessing the temperate phage GIL16 DNA replication machinery, which provides a powerful tool for continuous evolution in prokaryotic cells.

Henneberg et al. developed conformation-specific antibodies enabling probing NEDD8-activated cullin–RING ubiquitin E3 ligase networks in response to extracellular stimuli, metabolic signals and degrader drugs.

Biorefinery of waste biomass provides a sustainable route to produce chemicals and feedstocks. Now, the efficient production of free fatty acids and 3-hydroxypropionic acid from lignocellulose has been achieved via the co-utilization of xylose and glucose from lignocellulose using an engineered yeast.

Almost all terpenoids discovered so far have backbones made up of multiples of five carbon atoms. Here, the authors combine gene mining with biochemical characterization and chemical structure analysis to unveil an extensive class of terpenoids with 16 carbon atoms in bacteria.

NOXs are vital ROS-producing enzymes with roles in cell function and cancer. Here the authors combine computational and experimental methods to validate inhibitors for human NOX enzymes, opening avenues for redox biology-related cancer drug development.

A yeast platform for de novo biosynthesis of medicinal plant compounds has now been reported. The platform was used to explore the biocatalytic potential of refactored plant pathways and resulted in the production of 19 halogenated derivatives with therapeutic potential.