Nature’s Machinery, Repurposed: Expanding the Repertoire of Iron-Dependent Oxygenases

Iron is an especially important redox-active cofactor in biology because of its ability to mediate reactions with atmospheric O₂. Iron-dependent oxygenases exploit this earth-abundant transition metal for the insertion of oxygen atoms into organic compounds. Throughout the astounding diversity of transformations catalyzed by these enzymes, the protein framework directs reactive intermediates toward the precise formation of products, which, in many cases, necessitates the cleavage of strong C–H bonds. In recent years, members of several iron-dependent oxygenase families have been engineered for new-to-nature transformations that offer advantages over conventional synthetic methods. In this Perspective, we first explore what is known about the reactivity of heme-dependent cytochrome P450 oxygenases and nonheme iron-dependent oxygenases bearing the 2-His-1-carboxylate facial triad by reviewing mechanistic studies with an emphasis on how the protein scaffold maximizes the catalytic potential of the iron-heme and iron cofactors. We then review how these cofactors have been repurposed for abiological transformations by engineering the protein frameworks of these enzymes. Finally, we discuss contemporary challenges associated with engineering these platforms and comment on their roles in biocatalysis moving forward

Nature’s Machinery, Repurposed: Expanding the Repertoire of Iron-Dependent Oxygenases

Iron is an especially important redox-active cofactor in biology because of its ability to mediate reactions with atmospheric O₂. Iron-dependent oxygenases exploit this earth-abundant transition metal for the insertion of oxygen atoms into organic compounds. Throughout the astounding diversity of transformations catalyzed by these enzymes, the protein framework directs reactive intermediates toward the precise formation of products, which, in many cases, necessitates the cleavage of strong C–H bonds. In recent years, members of several iron-dependent oxygenase families have been engineered for new-to-nature transformations that offer advantages over conventional synthetic methods. In this Perspective, we first explore what is known about the reactivity of heme-dependent cytochrome P450 oxygenases and nonheme iron-dependent oxygenases bearing the 2-His-1-carboxylate facial triad by reviewing mechanistic studies with an emphasis on how the protein scaffold maximizes the catalytic potential of the iron-heme and iron cofactors. We then review how these cofactors have been repurposed for abiological transformations by engineering the protein frameworks of these enzymes. Finally, we discuss contemporary challenges associated with engineering these platforms and comment on their roles in biocatalysis moving forward

Determinants of a transcriptionally competent environment at the GM-CSF promoter

Granulocyte macrophage-colony stimulating factor (GM-CSF) is produced by T cells, but not B cells, in response to immune signals. GM-CSF gene activation in response to T-cell stimulation requires remodelling of chromatin associated with the gene promoter, and these changes do not occur in B cells. While the CpG methylation status of the murine GM-CSF promoter shows no correlation with the ability of the gene to respond to activation, we find that the basal chromatin environment of the gene promoter influences its ability to respond to immune signals. In unstimulated T cells but not B cells, the GM-CSF promoter is selectively marked by enrichment of histone acetylation, and association of the chromatin-remodelling protein BRG1. BRG1 is removed from the promoter upon activation concomitant with histone depletion and BRG1 is required for efficient chromatin remodelling and transcription. Increasing histone acetylation at the promoter in T cells is paralleled by increased BRG1 recruitment, resulting in more rapid chromatin remodelling, and an associated increase in GM-CSF mRNA levels. Furthermore, increasing histone acetylation in B cells removes the block in chromatin remodelling and transcriptional activation of the GM-CSF gene. These data are consistent with a model in which histone hyperacetylation and BRG1 enrichment at the GM-CSF promoter, generate a chromatin environment competent to respond to immune signals resulting in gene activation

The Isotopic Composition of Strontium in Fossils from the Kendrick Shale, Kentucky

Author Institution: Department of Geology and Mineralogy, The Ohio State UniversityNine analyses of the isotopic composition of strontium in the carbonate shells of marine fossils from the Kendrick Shale (Lower Pennsylvanian) of Kentucky indicate an average 87Sr/86Sr ratio of 0.7086^O.OOOSS at the 95 percent confidence limit. This value is in satisfactory agreement with previous measurements by Peterman et al. (1970) and confirms that strontium in the oceans during Early Pennsylvanian time was anomalously enriched in radiogenic 87Sr, compared to that in earlier and later periods. The isotopic composition of strontium in skeletal clacium carbonate of cephalopods, gastropods, and brachiopods from the Kendrick Shale appears to be the same in spite of the different feeding habits of these animals

Women over 40, foreigners of color, and other missing persons in globalizing mediascapes: understanding marketing images as mirrors of intersectionality

Media diversity studies regularly invoke the notion of marketing images as mirrors of racism and sexism. This article develops a higher-order concept of marketing images as “mirrors of intersectionality.” Drawing on a seven-dimensional study of coverperson diversity in a globalizing mediascape, the emergent concept highlights that marketing images reflect not just racism and sexism, but all categorical forms of marginalization, including ableism, ageism, colorism, fatism, and heterosexism, as well as intersectional forms of marginalization, such as sexist ageism and racist multiculturalism. Fueled by the legacies of history, aspirational marketing logics, and an industry-wide distribution of discriminatory work, marketing images help to perpetuate multiple, cumulative, and enduring advantages for privileged groups and disadvantages for marginalized groups. In this sense, marketing images, as mirrors of intersectionality, are complicit agents in the structuration of inequitable societies

Modulation of interleukin 2 high affinity binding to human T cells by a pyrimidodiazepine insect metabolite

AbstractAn insect metabolite containing the little known pyrimido[4,5-b][l,4]diazepine ring system has been found to act as an effective mimic of tetrahydrobiopterin in its ability to modulate the affinity of interleukin 2 (IL-2) for its receptors on human T cells. Semi-empirical molecular orbital calculations reveal that while tetrahydrobiopterin has considerable flexibility, the pyrimidodiazepine has rather few conformational options and offers a useful model for exploring the nature of the pterin binding site

Atomic Data Revisions for Transitions Relevant to Observations of Interstellar, Circumgalactic, and Intergalactic Matter

Measurements of element abundances in galaxies from astrophysical spectroscopy depend sensitively on the atomic data used. With the goal of making the latest atomic data accessible to the community, we present a compilation of selected atomic data for resonant absorption lines at wavelengths longward of 911.753 Å (the H I Lyman limit), for key heavy elements (heavier than atomic number 5) of astrophysical interest. In particular, we focus on the transitions of those ions that have been observed in the Milky Way interstellar medium (ISM), the circumgalactic medium (CGM) of the Milky Way and/or other galaxies, and the intergalactic medium (IGM). We provide wavelengths, oscillator strengths, associated accuracy grades, and references to the oscillator strength determinations. We also attempt to compare and assess the recent oscillator strength determinations. For about 22% of the lines that have updated oscillator strength values, the differences between the former values and the updated ones are ≳ 0.1 dex. Our compilation will be a useful resource for absorption line studies of the ISM, as well as studies of the CGM and IGM traced by sight lines to quasars and gamma-ray bursts. Studies (including those enabled by future generations of extremely large telescopes) of absorption by galaxies against the light of background galaxies will also benefit from our compilation

A purely kinetic description of the evaporation of water droplets

The process of water evaporation, although deeply studied, does not enjoy a kinetic description that captures known physics and can be integrated with other detailed processes such as drying of catalytic membranes embedded in vapor-fed devices and chemical reactions in aerosol whose volumes are changing dynamically. In this work, we present a simple, three-step kinetic model for water evaporation that is based on theory and validated by using well-established thermodynamic models of droplet size as a function of time, temperature, and relative humidity as well as data from time-resolved measurements of evaporating droplet size. The kinetic mechanism for evaporation is a combination of two limiting processes occurring in the highly dynamic liquid-vapor interfacial region: direct first order desorption of a single water molecule and desorption resulting from a local fluctuation, described using third order kinetics. The model reproduces data over a range of relative humidities and temperatures only if the interface that separates bulk water from gas phase water has a finite width, consistent with previous experimental and theoretical studies. The influence of droplet cooling during rapid evaporation on the kinetics is discussed; discrepancies between the various models point to the need for additional experimental data to identify their origin

Diffusion and reactivity in ultraviscous aerosol and the correlation with particle viscosity

Direct comparison of diffusion coefficients and viscosities of ternary component single aerosol particles levitated using optical tweezers.</p