Viral RNA molecules contain multiple layers of regulatory information. This includes features beyond the primary sequence, such as RNA structures and RNA modifications, including N6-methyladenosine ...(m6A). Many recent studies have identified the presence and location of m6A in viral RNA and have found diverse regulatory roles for this modification during viral infection. However, to date, viral m6A mapping strategies have limitations that prevent a complete understanding of the function of m6A on individual viral RNA molecules. While m6A sites have been profiled on bulk RNA from many viruses, the resulting m6A maps of viral RNAs described to date present a composite picture of m6A across viral RNA molecules in the infected cell. Thus, for most viruses, it is unknown if unique viral m6A profiles exist throughout infection, nor if they regulate specific viral life cycle stages. Here, we describe several challenges to defining the function of m6A in viral RNA molecules and provide a framework for future studies to help in the understanding of how m6A regulates viral infection.
Viral RNA molecules contain multiple layers of regulatory information. This includes features beyond the primary sequence, such as RNA structures and RNA modifications, including N6-methyladenosine ...(m
A). Many recent studies have identified the presence and location of m
A in viral RNA and have found diverse regulatory roles for this modification during viral infection. However, to date, viral m
A mapping strategies have limitations that prevent a complete understanding of the function of m
A on individual viral RNA molecules. While m
A sites have been profiled on bulk RNA from many viruses, the resulting m
A maps of viral RNAs described to date present a composite picture of m
A across viral RNA molecules in the infected cell. Thus, for most viruses, it is unknown if unique viral m
A profiles exist throughout infection, nor if they regulate specific viral life cycle stages. Here, we describe several challenges to defining the function of m
A in viral RNA molecules and provide a framework for future studies to help in the understanding of how m
A regulates viral infection.
The combination of biocatalysis and chemo‐catalysis increasingly offers chemists access to more diverse chemical architectures. Here, we describe the combination of a toolbox of ...chiral‐amine‐producing biocatalysts with a Buchwald–Hartwig cross‐coupling reaction, affording a variety of α‐chiral aniline derivatives. The use of a surfactant allowed reactions to be performed sequentially in the same flask, preventing the palladium catalyst from being inhibited by the high concentrations of ammonia, salts, or buffers present in the aqueous media in most cases. The methodology was further extended by combining with a dual‐enzyme biocatalytic hydrogen‐borrowing cascade in one pot to allow for the conversion of a racemic alcohol to a chiral aniline.
A two‐step, one‐pot chemoenzymatic synthesis of chiral anilines is reported. Chiral‐amine‐producing biocatalysts have been combined in the same pot as a Pd catalyst to allow the direct conversion of prochiral and racemic starting materials to enantiopure anilines. The use of a surfactant to enable this one‐pot process is a first for biocatalysis.
In this issue, Tapescu et al.1 identify DDX39A as a novel antiviral protein that acts on conserved features of alphavirus RNA to limit infection in an IFN-independent manner.
The pharmaceutical industry, driven by an increasing need to deliver new and more effective medicines to patients, is increasingly turning to the use of engineered biocatalysts for both lead ...generation of active compounds and the sustainable manufacture of active pharmaceutical ingredients. Advances in enzyme discovery, high-throughput screening and protein engineering have substantially expanded the available biocatalysts, and consequently, many more synthetic transformations are now possible. Enzymes can be fine-tuned for practical applications with greater speed and likelihood of success than before, thereby leading to greater predictability and confidence when scaling up these processes. Coupled with a greater awareness of which reactions are suitable for biocatalysis (for example, biocatalytic retrosynthesis), new chemoenzymatic and multi-enzyme processes have been designed and applied to the synthesis of a range of important pharmaceutical target molecules. Increasingly, researchers are exploring opportunities for using immobilized biocatalysts in flow conditions. In this Review, we discuss some of the key drivers and scientific developments that are expanding the application of biocatalysis in the pharmaceutical industry and highlight potential future developments that likely will continue to increase the impact of biocatalysis in drug development.Engineered biocatalysts are increasingly being used for both the identification and manufacture of active pharmaceutical ingredients. Here, the authors review key developments that are expanding the use of biocatalysis in the pharmaceutical industry.
Large and severe wildfires are an observable consequence of an increasingly arid American West. There is increasing consensus that human communities, land managers, and fire managers need to adapt ...and learn to live with wildfires. However, a myriad of human and ecological factors constrain adaptation, and existing science-based management strategies are not sufficient to address fire as both a problem and solution. To that end, we present a novel risk-science approach that aligns wildfire response decisions, mitigation opportunities, and land management objectives by consciously integrating social, ecological and fire management system needs. We use fire-prone landscapes of the US Pacific Northwest as our study area, and report on and describe how three complementary risk-based analytic tools-quantitative wildfire risk assessment, mapping of suppression difficulty, and atlases of potential control locations-can form the foundation for adaptive governance in fire management. Together, these tools integrate wildfire risk with fire management difficulties and opportunities, providing a more complete picture of the wildfire risk management challenge. Leveraging recent and ongoing experience integrating local experiential knowledge with these tools, we provide examples and discuss how these geospatial datasets create a risk-based planning structure that spans multiple spatial scales and uses. These uses include pre-planning strategic wildfire response, implementing safe wildfire response balancing risk with likelihood of success, and alignment of non-wildfire mitigation opportunities to support wildfire risk management more directly. We explicitly focus on multi-jurisdictional landscapes to demonstrate how these tools highlight the shared responsibility of wildfire risk mitigation. By integrating quantitative risk science, expert judgement and adaptive co-management, this process provides a much-needed pathway to transform fire-prone social ecological systems to be more responsive and adaptable to change and live with fire in an increasingly arid American West.
DNA charge transport chemistry offers a means of long-range, rapid redox signaling. We demonstrate that the 4Fe4S cluster in human DNA primase can make use of this chemistry to coordinate the first ...steps of DNA synthesis. Using DNA electrochemistry, we found that a change in oxidation state of the 4Fe4S cluster acts as a switch for DNA binding. Single-atom mutations that inhibit this charge transfer hinder primase initiation without affecting primase structure or polymerization. Generating a single base mismatch in the growing primer duplex, which attenuates DNA charge transport, inhibits primer truncation. Thus, redox signaling by 4Fe4S clusters using DNA charge transport regulates primase binding to DNA and illustrates chemistry that may efficiently drive substrate handoff between polymerases during DNA replication.
The Emergency Management Sector Adaptation Plan (EM-SAP) is a direct response to observed and projected effects of climate change and helps the sector identify opportunities and meet the risks ...communities face.
The NADPH‐dependent secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus (TeSADH), displaying broad substrate specificity and low enantioselectivity, was engineered to accept NADH as a ...cofactor. The engineered TeSADH showed a >10 000‐fold switch from NADPH towards NADH compared to the wildtype enzyme. This TeSADH variant was applied to a biocatalytic hydrogen‐borrowing system that employed catalytic amounts of NAD+, ammonia, and an amine dehydrogenase, which thereby enabled the conversion a range of alcohols into chiral amines.
Designed to share: Rational engineering of the cofactor dependence in a nonselective alcohol dehydrogenase opens the door to a second generation of hydrogen‐borrowing enzyme cascades for the amination of alcohols.
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![The [4Fe4S] cluster of huma...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0036-8075/small "The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport")
