Reviews & Analysis

Understanding the mechanisms by which gut metabolites impact host physiology should help understand a variety of disease associated with gut-microbiota dysbiosis. A review of this microbial impact in both invertebrate and vertebrate highlights roles in energy harvest, pathogen resistance and the development of allergic and neurological disorders.

The finding that the antifungal activity of amphotericin B is primarily due to its ability to extract ergosterol from fungal membranes suggests a new rationale for drug design, which should lead to advanced treatments, particularly for invasive fungal infections.

Itaconate is a metabolite secreted by activated macrophages that inhibits pathogen growth. Some pathogens use itaconate degradation enzymes to promote their survival and infectivity, highlighting metabolic pathways to be considered in host-pathogen interactions.

A bioorthogonal decaging strategy, mediated by small-molecule palladium compounds, can recover the lysine-dependent activity of cellular proteins. This activation technique could be generally applicable for controlling and probing function of a protein target in living cells.

Maintenance of the pluripotent stem cell state is regulated by the post-translational modification of histones. The discovery that citrullination of the linker histone H1 is critical to this process represents a new role for the protein arginine deiminases in development.

Methane is an energy resource that is currently being wasted through emissions, venting and flaring during petroleum extraction. Recent discoveries regarding the basis of enzyme function and microbial metabolism provide the foundation for new thinking about how to reclaim this resource through bioconversion.

The addition of polysialic acid to proteins and cells is emerging as a promising therapeutic strategy. Polysialyltransferases synthesize polymers of widely varying lengths not optimal for therapeutic reagents, but the development of enzyme variants using neutral genetic drift offers a new way to overcome this problem.

An inhibitor of the deubiquitinase complex USP1-UAF1 highlights the requirement for reversible ubiquitination in DNA repair pathways that are critical for human development and disease.

Coenzyme Q₁₀ is an essential lipid in aerobic respiratory metabolism and a membrane antioxidant. A new function is revealed for CoQ; as a membrane-stabilizing agent that enhances resistance of bacterial cell and liposome membranes to salt stress.

Probe molecules with systemic activity remain rare, and, as was realized in the pre-molecular era, even their off-target activity can illuminate biology. A study reporting a screen of over 600 kinase inhibitors found nine with bromodomain inhibitory activity and has implications for mechanism and compound optimization.

Metabolically engineered cells are yielding an expansion of specialty chemicals that rival or supplement traditional petroleum-derived chemicals. New results establish a biosynthetic route to volatile esters and larger acetate esters equivalent in size to biodiesel, providing an intriguing new direction to create fragrances, chemicals or fuels.

System-wide approaches are gaining popularity over traditional studies of individual molecular components. A new NMR approach unravels the interaction hierarchy of these different components by placing them in direct competition for the same target.

TRPM3 can permeate ions through two distinct pores—the central pore and a likely alternative 'omega pore'. Entry of ions through the alternative pore of TRPM3 contributes to pain generation, making it an attractive target for the design of new analgesics.

The bacterial halogenase SyrB2 catalyzes selective installation of halogens in place of unactivated aliphatic C-H bonds. By substituting halide reagents with the nitrogenous anions N₃⁻ and NO₂⁻, SyrB2 can perform C-N bond formation reactions not previously observed in nature.

The mitochondrial permeability transition pore (mPTP) is a multiprotein complex that regulates cell death in multiple pathological conditions. The discovery of new critical components of the mPTP and the identification of anticancer drugs acting on mPTP opens new frontiers for mitochondrial medicine.

Stem cell therapeutics hold great promise, but obtaining optimal cell populations for transplantation remains a major challenge. High-throughput screens of zebrafish embryonic cells have enabled identification of small molecules that can direct the fate of pluripotent stem cells toward tissue-specific progenitors with high therapeutic potential.