Spotlight Cite This: ACS Chem. Biol. 2018, 13, 842−843
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he 2018 ACS Spring National Meeting in New Orleans featured many outstanding sessions in chemical biology, and we were proud to have our ACS Chemical Biology Lectureship symposium, cosponsored by the ACS Division of Biological Chemistry, among them. Each year, the award honors an investigator who has made outstanding contributions to the field of chemical biology. Previous recipients include Alanna Schepartz (2010), Stuart Schreiber (2011), Carolyn Bertozzi (2012), Wilfred van der Donk (2013), Peter Dervan (2014), Kevan Shokat (2015), Peter G. Schultz (2016), and Benjamin F. Cravatt (2017). In addition to a keynote lecture from the awardee, the symposium is also an opportunity to highlight exciting research from young investigators. This year’s award honored Jim Wells, who holds the Harry Wm. and Diana V. Hind Distinguished Professorship in Pharmaceutical Sciences at the University of California, San Francisco. The symposium also featured presentations from four rising stars in chemical biology: Emily Balskus (Harvard University), Kamil Godula (University of California, San Diego), Bo Li (University of North Carolina at Chapel Hill), and Pamela Peralta-Yahya (Georgia Institute of Technology). Moderated by Editor-in-Chief Laura Kiessling, the session was a vibrant compendium of cutting edge research at the intersection of chemistry and biology.
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DECIPHERING THE HUMAN MICROBIOTA USING CHEMISTRY The session was kicked off with a talk from Emily Balskus, Morris Kahn Associate Professor of Chemistry and Chemical Biology at Harvard. Her research program seeks to elucidate the mechanisms underlying human gut microbial processes by connecting elements of microbiota metabolism to specific genes, enzymes, and organisms. Noting the distinct chemical differences between human and microbial drug metabolism microbe metabolism is reductive and hydrolyticBalskus detailed how her group and collaborators used a transcriptomic-based strategy to identify the microbial enzymes that metabolize, and thus inactivate, drugs used in the treatment of human disease. Transcriptional profiling also revealed genes and organisms linked to microbial metabolic activity along the gut−brain axis, which can have clinical relevance for patients.
Editor-in-Chief Laura Kiessling and ACS Chemical Biology Lectureship awardee Jim Wells. Photo courtesy of David Liu.
glycocalyx. The development of mimetic glycosaminoglycan polymers enabled effective remodeling of the glycocalyx and induction of neural differentiation in embryonic stem cells. Glycocalyx engineering has broad applications in cell differentiation and opens exciting avenues for the role that chemical biology can play in regenerative medicine and beyond.
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MIGHTY CHEMISTRY OF BACTERIAL SMALL MOLECULES Big things come in small packages, especially when it comes to bacterial metabolites. Bo Li, Assistant Professor of Chemical Biology and Natural Product Biosynthesis and Discovery at UNC Chapel Hill, demonstrated as much during her lecture: tiny pharmacomores with simple structures, such as holomycin and other dithiolopyrrolones, can have powerful antibiotic activity. Her group elucidated the bacterial biosynthetic and metabolic mechanisms that afford dithiolopyrrolones their antimicrobial properties and employed a chemical genomics approach to identify its targets. Their studies revealed that holomycin disrupts metal homeostasis in the cell, through
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CHEMICAL EDITING OF THE GLYCOCALYX TO INFLUENCE CELLULAR FUNCTION The next speaker was Kamil Godula, Assistant Professor of Chemistry and Biochemistry at UCSD, whose research program focuses on manipulating and engineering the glycocalyx, a complex system of glycolipids, proteoglycans, and receptor complexes on the surface of the cell. The glycocalyx is involved in many key biological processes, such as cell−cell communication, cellular differentiation, and host− pathogen interactions. Godula described the assembly of synthetic glycomaterials to mimic various components of the © 2018 American Chemical Society
Published: April 20, 2018 842
DOI: 10.1021/acschembio.8b00301 ACS Chem. Biol. 2018, 13, 842−843
ACS Chemical Biology
Spotlight
binding and inactivation of an essential Zn enzyme and metallo−β-lactamase, as well as through direct metal binding. Li’s talk demonstrated how these high-throughput screening methods enable a deeper understanding of how antibiotics function and open doors for the identification of potential new antibiotics with simple yet unusual structures.
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GPCR-BASED SENSORS TO ACCELERATE THE ENGINEERING OF CHEMICAL-PRODUCING MICROBES Microbial metabolism emerged as a major theme throughout this session, as Pamela Peralta-Yahya, Assistant Professor of Chemistry and Biochemistry at Georgia Tech, presented on her group’s work engineering biosensors that can rapidly detect the chemical products produced by designer microbes in high throughput screens. The evolutionary engineering of microbes that can produce chemicals in high volumes offers new avenues for the production of biofuels. However, current chromatographic-based methods for evaluating these bioproducts cause a bottleneck in identifying effective chemical-producing microbes. Peralta-Yahya’s group exploited the intrinsic chemical-sensing properties of G-protein coupled receptors (GPCRs) to engineer GPCR-based yeast biosensors that can rapidly detect fatty acids, key precursors for biofuels and other industrial chemical products, produced by the cell.
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DETECTING AND ATTACKING CANCER SURFACE-OMES WITH RECOMBINANT ANTIBODIES The keynote lecture of the session was given by ACS Chemical Biology Lectureship awardee Jim Wells, where he discussed the cell surface proteome (surface-ome), an essential platform for cell−cell communications. The cellular changes caused by oncogenesis may also impact the cell surface-ome, making it a potential therapeutic target in the treatment of various cancers. The Wells group used a combination of proteomic and transcriptomic techniques to profile changes to the cell surface proteome induced by the expression of oncogenic KRas. They also employed genetically barcoded antibodies for highly multiplexed surface-ome profiling. Together, these techniques allowed mapping of the KRas cell surface, enabling the identification of cell surface proteins that are unique to cancer cells and thus possible therapeutic targets. Wells and coworkers also generated chemical-epitope-selective antibodies that can act as antibody-based chemically induced dimerizers for the regulation of human cancer cell therapies. The ACS Chemical Biology Lectureship symposium was followed by a symposium in honor of David Liu, Professor of Chemistry and Chemical Biology at Harvard University and recipient of the Ronald Breslow Award for Achievement in Biomimetic Chemistry. This award symposium contained more outstanding talks from chemical biologists, including Gerald Joyce and previous Lectureship awardees Stuart Schreiber and Pete Schultz.
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DOI: 10.1021/acschembio.8b00301 ACS Chem. Biol. 2018, 13, 842−843
