Eli Lilly Award in Biological Chemistry

Professor Neal K. Devaraj, University of California, San Diego

For outstanding research in biological chemistry of unusual merit and independence of thought and originality.

Professor Neal K. Devaraj is the recipient of the 2019 Eli Lilly Award in Biological Chemistry. One of the most challenging questions in chemical biology is how non-living matter, such as simple organic molecules, can assemble to form life. The Devaraj group is approaching this problem through the synthesis of artificial cells, developing coupling reactions that drive the self-assembly, growth and reproduction of lipid vesicle assemblies. To guide the work, they are developing chemical tools to blueprint the structure and function of modern cells. Using this combined approach, the lab strives to understand the prerequisite chemistry from which biology can emerge.

Devaraj and his lab synthesized the first artificial cell membrane that can sustain continual growth. Unlike natural membranes, biomimetic systems cannot maintain growth owing to an inability to replenish phospholipid-synthesizing catalysts that are diluted during lipid expansion. The Devaraj lab created an artificial cell membrane that continually synthesizes all of the components needed to form additional catalytic membranes. Membrane growth can proceed indefinitely as the catalyst required for vesicle growth also autocatalyzes its own synthesis.

Another direction of his lab seeks to develop new tools for labeling and manipulating RNA. Mainstream methods for studying RNA utilize non-covalent interactions between the probes and the RNA of interest, which limits their robustness, especially for less abundant RNA targets. The Devaraj lab devised a method for the site-specific covalent labeling of RNA with functional reporters in a single conjugation step by exploiting a bacterial tRNA modifying enzyme, tRNA-guanine transglycosylase (TGT), and unnatural analogs of its native substrate preQ1. RNA transglycosylation at guanosine (RNA-TAG) can incorporate a wide variety of probes targeted to a minimal 17-residue hairpin that can be encoded on any RNA. The use of covalent linkages will lead to robust methods to isolate RNA and label RNA.

Applying the lessons learned from their earlier work in chemoselective lipid synthesis, his lab has recently developed traceless chemistries to assemble lipid natural products from within living cells. This approach allows unequivocal association of specific lipids generated in vivo with their cellular function. His lab’s initial studies have focused on generating ceramides, one of the most enigmatic classes of molecules within the realm of bioactive lipids. The Devaraj lab found that delivery of fully saturated ceramides significantly reduces cell viability while there is no reduction in cell viability following delivery of monounsaturated ceramides. These observations highlight the importance of species-specific study of ceramides and demonstrate the power of chemical tools to circumvent the limitations of endogenous lipid synthesis pathways to uncover the function of individual lipid molecules in vivo.

Pfizer Award in Enzyme Chemistry

Professor Kenichi Yokoyama, Duke University

For outstanding work in enzyme chemistry where the presence of enzyme action is unequivocally demonstrated.

Professor Kenichi Yokoyama is the recipient of the 2019 Pfizer Award in Enzyme Chemistry in recognition of his contributions to the elucidation of complex mechanisms and novel functions of enzymes involved in the biosynthesis of cofactors and natural products. One area of focus of the Yokoyama group has been radical-mediated enzyme catalysis. In the past decade, the scope of free radical reactions in enzymology has expanded significantly. In particular, a multitude of enzymes in the radical S-adenosyl-L-methionine (SAM) superfamily have been found to catalyze highly diverse and chemically challenging reactions. The main focus of the Yokoyama lab has been radical SAM enzymes involved in C–C bond formation during the biosynthesis of the carbon skeletons of cofactors and natural products. One of their most significant areas of contribution is elucidation of the mechanism of pterin backbone construction during molybdenum cofactor (Moco) biosynthesis, a pathway linked to a fatal metabolic disorder in humans and bacterial pathogenicity. In this study, the Yokoyama group characterized the radical SAM enzyme, MoaA, along with MoaC, another enzyme in the pathway, and identified a structurally novel cryptic biosynthetic intermediate, 3’,8-cH2GTP. Together with subsequent mechanistic studies, their results elucidated the functions of both MoaA and MoaC for the first time in the >30 years-long history of the study of Moco biosynthesis. Another area of Yokoyama lab contribution is the functional characterization of the radical SAM enzyme NikJ in the biosynthesis of antifungal nucleoside antibiotics such as the nikkomycins and polyoxins. In this study, NikJ was found to catalyze formation of the unique bicyclic nucleotide, octosyl acid 5’-phosphate, through radical-mediated C-C bond formation involving a redox-active Cys residue. This revelation allowed the Yokoyama lab to perform bioinformatic analyses of related pathways, which suggested potentials for genome mining discovery of novel antifungal nucleoside natural products. In both of these studies, radical SAM enzymes were found to install C-C bonds in unique positions within precursors. The lab is currently extending their efforts to the other steps of the pathways and the mechanism of action of antifungal natural products. The Yokoyama lab studies have expanded our understanding of carbon skeleton construction in metabolic pathways and demonstrated the impact of identifying novel enzyme functions and mechanisms on future development of novel therapeutics for infectious and metabolic diseases.

The Repligen Award in Chemistry of Biological Processes

This award is no longer supported.  Division members are working to establish new funding in order to continue this tradition honoring luminary biochemists who have shaped our field.  If you would be willing to help, or know of possible sources of support for this long-standing award, please contact the division via Wayne Outten (OUTTENF@mailbox.sc.edu) or Anne-Frances Miller (afmill3r2@gmail.com).  Thank you.

Gordon Hammes ACS Biochemistry Lectureship

Professor Dan Kahne, Harvard University

For outstanding contributions in scientific research at the interface of chemistry and biology, particularly in the realm of biochemistry, biological chemistry and molecular biology.

Professor Dan Kahne is the recipient of the 2019 Gordon Hammes ACS Biochemistry Lectureship. The Gordon Hammes Lecture Award is sponsored jointly by Biochemistry and the ACS Division of Biological Chemistry. The objective is to recognize and honor a single individual whose scientific contributions have had a significant impact on research at the interface of chemistry and biology. This year’s award goes to Professor Dan Kahne of Harvard University.

Professor Kahne trained with Gilbert Stork at Columbia University and started his independent career as a synthetic chemist where he developed a novel method to make glycosidic linkages for use in complex carbohydrate synthesis. His laboratory has a long-standing interest in natural products and their targets. They were the first to develop synthetic methods to change the natural carbohydrates attached to vancomycin, allowing them to make derivatives of vancomycin that kill vancomycin-resistant bacteria. These studies of glycopeptide antibiotics led to a longstanding quest to understand the extracellular steps of cell wall synthesis in detail. They have synthesized the lipid-linked oligosaccharide building blocks of peptidoglycan and developed sophisticated assays to study the penicillin binding proteins that polymerize and crosslink peptidoglycan. Since both Gram-positive and Gram-negative bacteria are surrounded by peptidoglycan, which is essential for survival, it is a major target for antibiotics. Many of the tools they have developed are useful to both discover new antibiotics and to dissect their mechanism of action.

In addition to expertise in synthesis and mechanistic studies of antibiotics, the Kahne group has considerable understanding of the physiology of Gram-negative bacteria. Gram-negative bacteria depend for their survival on having an intact outer membrane. It is the defining piece of physiology that differentiates Gram-negative from Gram-positive organisms and its presence serves as an effective permeability barrier that prevents penetration of most drugs. This outer membrane is assembled by several multi-protein machines, and his group identified many of the genes responsible for inserting beta-barrel proteins into the outer membrane as well as several of the genes involved in assembling lipopolysaccharide on the cell surface of this outer membrane. His lab has purified the components of both multi-protein complexes and reconstituted their activity in vitro in proteoliposomes, opening the door for detailed biochemical analysis. They are now in a position to use these tools as part of a program to discover inhibitors of outer membrane biogenesis, which would make the cells leaky. Such OM assembly inhibitors could be effective alone or used in combination with known antibiotics to treat problematic Gram-negative infections (ESKAPE pathogens).

Kahne will present a talk and receive his award during the Gordon Hammes ACS Biochemistry Symposium at the 258th ACS National Meeting & Exposition, held in San Diego, Aug. 25-29, 2019.

Gordon Hammes ACS Biochemistry Scholar Award

Professor Kathleen Leamy, Gonzaga University

To honor the young scientists responsible for the very best papers published in Biochemistry.

Professor Kathleen Leamy is the recipient of the 2019 Gordon Hammes Scholar Award. The Gordon Hammes Scholar Award honors the young scientists responsible for the very best papers published in Biochemistry. Established in 2017 and awarded alongside the Gordon Hammes Lectureship Award, the Scholar Award seeks to recognize those at the bench – graduate students, postdocs, and undergraduates – for the outstanding work they do. The award is sponsored jointly by Biochemistry and the ACS Division of Biological Chemistry. Professor Leamy of Gonzaga University was selected as this year’s winner from a large applicant pool based on her first-author paper, “Molecular Mechanism for Folding Cooperativity of Functional RNAs in Living Organisms,” published earlier this year.

Kathleen Leamy grew up in New York State and received her bachelor’s degree from Siena College, with majors in chemistry and biochemistry.  While at Siena College she did research with Dr. Daniel Moriarty and Dr. Jodi O’Donnell, where she studied natural product antibiotics and porphyrin thin films sensors.  Kathleen completed her doctoral degree at The Pennsylvania State University under the direction of Dr. Philip Bevilacqua, studying the folding and adaptation of functional RNAs. She is currently an assistant professor in the Department of Chemistry and Biochemistry at Gonzaga University.

Leamy will present a talk describing her research and receive her award during the Gordon Hammes ACS Biochemistry Symposium at the 258th ACS National Meeting & Exposition, held in San Diego, Aug. 25-29, 2019.

The ACS Chemical Biology Lectureship

Professor Chuan He, University of Chicago

For contributions that have had a major impact on scientific research in the area of Chemical Biology.

The 2019 ACS Chemical Biology Lectureship Award was presented to Professor Chuan He. The award is sponsored jointly by ACS Chemical Biology and the ACS Division of Biological Chemistry. Professor He is the John T. Wilson Distinguished Service Professor in the Department of Chemistry and Department of Biochemistry and Molecular Biology at the University of Chicago. His recent accomplishments are vast. In 2011, his group discovered reversible RNA methylation as a new mechanism of gene expression regulation at the post-transcriptional level. Since then, he has been selected as an investigator of the Howard Hughes Medical Institute (2013), leads Chicago’s first Center for Excellence in Genomic Science (2016), and was one of three recipients of the Paul Marks Prize for Cancer Research from Memorial Sloan Kettering (2017).

Professor He received his Bachelor of Science degree in 1994 from the University of Science and Technology of China and his Ph.D. in Chemistry from the Massachusetts Institute of Technology in 2000. After training as a Damon-Runyon postdoctoral fellow at Harvard University, he joined the University of Chicago as an assistant professor, rising to associate professor in 2008 and full professor in 2010. His recent research concerns reversible RNA and DNA methylation in biological regulation. His laboratory has spearheaded the development of enabling technologies to study the biology of 5-hydroxymethylcytosine (5hmC) in mammalian genomes. Dr. He presented his work on April 2, 2019 at the 257th ACS National Meeting and Exposition held in Orlando, Florida.

The Biopolymers Murray Goodman Memorial Prize

Professor David Beratan, Duke University

For outstanding accomplishments in one or more of the areas of biochemistry, biophysical chemistry, biophysics, and/or chemical biology.

Professor David Beratan is the recipient of the 2018 Biopolymers Murray Goodman Memorial Prize for his seminal contributions to the field of electron transfer in biological systems. Dr. Beratan is currently the R. J. Reynolds Professor of Chemistry in the Department of Chemistry at Duke University and holds Professorships in the Departments of Physics and Biochemistry at Duke. He is also an Adjunct Professor in the Department of Chemistry of the University of Pittsburgh. Gaining an undergraduate degree in chemistry from Duke University and a Ph.D. from California Institute of Technology, Professor Beratan went on to work at NASA’s Jet Propulsion Laboratory and the University of Pittsburgh before returning to Duke in 2001.

Professor Beratan’s theoretical insights into tunnelling pathways of electron transfer in biological macromolecules established physical principles that have been extended to understand the phenomenon in a wide range of systems. His research group works closely with experimentalists and some of the current foci are designing molecular structures and assemblies for solar energy capture and conversion, exploring charge transfer mechanisms in bacterial nanowires and designing de novo proteins to explore proton-coupled electron transfer mechanisms. Professor Beratan presented his work in April 2019 at the 257th ACS National Meeting and Exposition held in Orlando, Florida.