Crystal structures and activity assays with modified substrates provide new insights into O-GlcNAc transferase’s elusive reaction coordinate. This cartoon shows a rendition of OGT’s reaction trajectory in an overlay of the protein with ternary substrates and ternary products. Cover art by Erin Dewalt, based on imagery from Michael Lazarus. Brief Communication, p966; Article, p969; News & Views, p952

Cancer mutations lead to a variety of outcomes, including—for isocitrate dehydrogenase—gains of function unique from that of the parent molecule. A new design strategy transplants these activating mutations into a homologous protein to deliver a new enzyme function and a biocatalytic intermediate to the commodity chemical adipic acid. This composite shows the transfer of mutational information from anaplastic oligodendroglioma through to an adipic acid–derived nylon fabric. Cover art by MaryLou Quillen, based on imagery from Zachary Reitman, Steven Conlon and Roger McLendon. Brief Communication, p887; News & Views, p874

The phospholipid transacylase tafazzin selects lipid substrates on the basis of the physical properties of the membrane domains in which it is active, preferring lipids in the inverted hexagonal phase, representing curved or hemifused membrane zones. This concept of segregation of activity is captured as a polarizing microscope image of a cooling liquid crystal emerging from an isotropic melt, which reveals a dark phase where there is no spatial arrangement of the molecules and periodic stripes in the liquid crystal regions where molecules tend to be parallel to each other, forming helices. Cover art by MaryLou Quillen, based on an image from Bohdan Senyuk and Oleg D. Lavrentovich. Article, p862

Basement membranes are a specialized extracellular matrix underlying epithelia that are composed of collagen IV networks, which in turn contain sulfilimine bonds between a methionine sulfur and a hydroxylysine nitrogen. Now, peroxidasin is shown to be the enzyme that catalyzes the formation of these unusual bonds via the production of hypohalous acid intermediates. The image shows the collagen network and a knot held together by sulfilimine bonds. Cover art by Erin Dewalt and MaryLou Quillen, based on an image from Joseph T. Roland. Article, p784; News & Views, p740

Phenylketonuria (PKU) is a metabolic disease characterized by increased phenylalanine in the blood and progressive mental retardation. Now, phenylalanine is shown to self-assemble into toxic amyloid fibrils at concentrations achieved in disease, and these fibrils accumulate in the brains of individuals with PKU and in mouse models of the disease. The image shows the elongated ordered phenylalanine assemblies stained with thioflavin T. Cover art by Erin Dewalt, based on an image from Lihi Adler-Abramovich. Article, p701

Plants use a hydrophobic cuticle made of cutin and waxes to protect themselves from the environment. Investigation of a tomato mutant deficient in cutin biosynthesis now reveals the first cutin synthase, capable of converting monomeric hydroxyacyl chains into polyesters. This image shows the cuticle (red) and polysaccharide cell wall (blue) of an M82 tomato cultivar. Cover art by Erin Dewalt, based on an image from Gregory Buda. Brief Communication, p609; News & Views, p603

Metabolism is moving beyond flat biochemical charts into three dimensions, where dynamics in time and space lead to distinct biological outcomes and manipulation of metabolic pathways has the potential to address medical and societal needs. This image shows how metabolic blueprints drawn from characterization of enzyme pathways, when shaped by a more comprehensive understanding of flux, regulation and organization, can be used to construct a complete cell. Cover art by Erin Dewalt, based on a KEGG metabolic pathway map used with permission from GenomeNet.

Bacteria use indole as a community signal to convert to a persistent state associated with antibiotic tolerance as well as chronic and recurrent infection. This image shows a cartoon of bacterial communication, including the emission and detection of indole in the surroundings. Cover art by Erin Dewalt, based on an image from Katie M. Flynn and Ahmad S. Khalil. Brief Communication, p431

Dissection of an HR-PKS ketoreductase demonstrates substrate length–dependent stereospecificity in enzyme function and identifies motifs responsible for substrate recognition during the biosynthesis of hypothemycin in Hypomyces subiculosus. This image shows a wild mushroom infected by Hypomyces sp. Cover art by Erin Dewalt, based on an image from J.J. Harrison. Brief Communication, p331; News & Views, p322

A bioinformatics analysis of untargeted metabolomic data defines N,N-dimethylsphingosine as a chemical trigger for neuropathic pain. This image depicts the metabolomic alignment process as performed by the bioinformatic software XCMS, superimposed on a neural synapse. Cover art by Erin Dewalt, based on an image from Gary Siuzdak and Gary Patti, using artwork with permission from Purdue Pharma L.P. Brief Communication, p232

Photoisomerization of the visual pigment chromophore 11-cis-retinal is the first step of vision, and this event produces all-trans-retinal, whose delayed clearance from the retina is linked to retinal degeneration. Maeda et al. show that compounds containing a primary amine can protect a mouse disease model from light-induced retinal degeneration by forming a transient Schiff base with all-trans-retinal. Shown is staining of a vertebrate retina consisting of several layers of differentiated neural cells, including rod (red) and cone (green) photoreceptors. Cover art by Erin Dewalt, based on an image from Krzysztof Palczewski. Article, p170

The ability of microorganisms such as bacteria to affect their hosts and cause disease highlights the importance of understanding microbial chemistry and biology and how microbes affect the chemistry and biology of their environment under various conditions, including within communities or when challenged by antimicrobial drugs. With an emphasis on bacteria, this issue features pieces aimed at exploring how microbes interact with their environment and how an understanding of their ecology and evolution can be exploited to generate new antimicrobials. Cover art by Erin Dewalt.