November 2011

Chemical biology and biocatalysis

meetings_chemical-biologyWhile it long has been appreciated that chemistry and biology are linked inextricably, scientists working today at the intersection between these disciplines are providing molecular resolution descriptions of complex biological phenomena and generating new tools that will transform the way we live. The symposium “Chemical biology and biocatalysis” at the 2012 ASBMB annual meeting highlights the work of prominent scientists whose work defines how chemical intuition and chemical tools can inform studies and applications of biological systems.

In a session titled “Metabolomics,” geneticist Michael Snyder will describe how a comprehensive, mass-spectrometry-based approach has revealed new insights into metabolite-protein interactions. This work is an extension of his groundbreaking work in high-throughput transcriptomics. Chemist Alan Saghatelian will discuss progress in the cataloging of metabolites and pathways. His group recently has identified monoalkylglycerol ethers as natural adipocyte differentiation factors and has explored the identification of endogenous ligands of nuclear hormone receptors using a systems approach. Plant biochemist Anne Osbourn will talk about her work on biosynthetic pathways of natural products in oats and rice. Her studies have uncovered how the complex and biomedically important small molecules often isolated from plants can be stitched together.

In “Chemistry and the Service of Medicine” pharmacologist Phil Cole will describe acyltransferases as possible targets in cancer and metabolism. Using rational design principles, his group has obtained preclinical data that selective synthetic agents can be identified for this difficult-to-inhibit enzyme family. Chemist Gabriela Chiosis will highlight the potential of protein chaperones, including heat-shock protein 90, as targets with significant clinical promise for the treatment of a variety of cancers. Her chemical-chaperone inhibitors are proving valuable tools for the exploration of this anticancer landscape. Chemist David Spiegel takes an unorthodox approach to generating immune response to cancer or infectious targets. By creating bivalent high-affinity ligands that interact with specific receptors found in neoplasms or pathogens on the one hand and immune complexes on the other, he is recruiting the immune response to specific cell types.

In “Metabolic Engineering: From Antibiotics to Biofuels,” biochemist Michael Thomas will present his studies of enzymes called polyketide synthases, which catalyze the biosynthesis of pharmacologically important antibiotics. His discoveries of noncanonical mechanisms of polyketide synthase catalysis inform the engineering of non-natural enzymes for drug synthesis. In a complementary talk, Christina Smolke will discuss her groundbreaking work in the engineering of yeasts to produce new variants of compounds normally produced by plants. These compounds, known as alkaloids, have potential to treat malaria and other maladies. Finally, Jason Sello will discuss his work on engineering soil-dwelling Streptomyces bacteria to convert plant biomass into high-value chemicals and fuels.

In the “Frontiers in Enzymology” session, biochemist Henning Lin, a leader in the field of post-translational modifications, will describe the molecular mechanisms by which dipthamide, the target of the diphtheria toxin, is biosynthesized. Structural biologist Chuan He will provide a molecular-resolution exposé of enzymes that use peculiar catalytic logic to repair DNA damage. The studies of Lin and He are characterized by ingenious integration of methods from chemistry and biology. Enzymologist David Cane has provided new insights into mechanistic enzymology via his mining of newly available microbial genome sequences. His analysis of novel and peculiar terpene synthases has provided new insights into startlingly sophisticated bond formations and skeletal rearrangements in the biosynthesis of medicinally and ecologically important metabolites.

Meetings_Chemical_Biology_coleMeetings_Chemical_biology_selloPhilip A. Cole (pcole@jhmi.edu) is the E.K. Marshall and Thomas H. Maren professor at Johns Hopkins University School of Medicine. Jason K. Sello (jason_sello@brown.edu) is an assistant professor at Brown University.


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