210 Washtenaw Ave
Ann Arbor, Michigan 48109-2216
Available to mentor
Professor Sherman received his undergraduate degree in chemistry at UC Santa Cruz and Ph.D. in synthetic organic chemistry at Columbia University with Gilbert Stork. After four years at Biogen, he moved to the John Innes Institute as a research scientist with Sir Prof. David A. Hopwood. Following 13 years at the University of Minnesota, Prof. Sherman moved to the University of Michigan and is now the Hans W. Vahlteich Professor of Medicinal Chemistry, Professor of Chemistry, and Professor of Microbiology & Immunology. Sherman’s laboratory is in the U-M Life Sciences Institute where his research focuses on the discovery and analysis of bioactive natural products, their metabolic pathways, and diverse biosynthetic enzymes. The functional, structural, and computational analysis of new biocatalysts for late-stage C-H functionalization, polyketide assembly, and pericyclic reactions is a particular focus of the group. Prof. Sherman is faculty lead for the U-M Natural Products Biosciences Initiative and co-founder of the Natural Products Discovery Core.
Dr. Sherman was founding Director of the Center for Chemical Genomics at the University of Michigan Life Science Institute (2004 – 2013). LSI maintains core facilities covering the areas of high throughput screening and drug discovery, structural biology and protein production with resources to support cross-disciplinary science including genetics; genomics and proteomics; molecular and cellular biology; and structural, chemical and computational biology. Sherman now serves on the advisory board for Michigan Drug Discovery.
Sherman Lab
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Postdoctoral FellowMassachusetts Institute of Technology, Center for Cancer Research, 1984
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PhDColumbia University, New York City, 1981
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BA ChemistryUniversity of California, Santa Cruz, Santa Cruz, 1978
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Center MemberSamuel and Jean Frankel Cardiovascular Center
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Center MemberCenter for Computational Medicine and Bioinformatics
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Center MemberRogel Cancer Center
I have committed over 30 years as an independent investigator to discovering the power and potential of previously unknown chemical compounds made by microorganisms in the natural world and using new technologies to test these compounds against novel targets involved in infectious diseases, cancer, and neurological disorders. My long-term goal in these efforts has been to create and identify promising new therapeutics to improve quality of life through the development of new drugs. My role in the proposed project will focus on developing new macrolide antibiotics in collaboration with Drs. Alan Healy and Emilia Oueis.
Following my initial training in natural product isolation and total synthesis, my research focus shifted toward understanding the genetic and biochemical basis for assembly and tailoring of complex, microbial derived secondary metabolites. This foundation continues to drive my laboratory to explore and identify new molecules from diverse bacterial and fungal sources, each bringing a unique opportunity to delineate the fascinating biological activities, biosynthetic pathways, enzymes, and multicomponent systems with remarkable catalytic properties. Since beginning my academic career in 1990, my laboratory has driven a series of cross-disciplinary projects, each bringing new perspectives to solve complex problems in the field. Our twenty-year development of a unique microbial natural product extract library (currently >50,000 samples from 10,000 pure culture microbes) is enabling the identification of a multitude of new bioactive metabolites.
Since 2004, I have worked across schools and units at U-M to build academic drug discovery capabilities, primarily in the Life Sciences Institute, where my lab is located and the library stored and maintained, and in the College of Pharmacy, where I hold tenure and teach. I was the inaugural director of the Center for Chemical Genomics, which provides high-throughput screening, and I am currently faculty Principal Investigator of the U-M Natural Products Biosciences Initiative, which advances compounds and their derivatives toward the clinic.
U-M represents an exceptionally collaborative and stimulating environment for my research, teaching and outreach/service activities. Since joining the Life Sciences Institute, I have mentored an outstanding and diverse group of chemists, chemical biologists, and microbial biochemists, many of whom have become leaders in their field. During my academic career, I have mentored 67 Ph.D. students, 60 postdoctoral fellows and >85 undergraduates in my laboratory. My engagement in several graduate and NIH training programs has provided an outstanding forum to advise many students in cross-disciplinary research, and career development. Natural product sciences is a global enterprise, and I have advanced research collaborations in numerous countries, teaching short courses, and hosting a diversity of international students, including undergraduates, Ph.D. candidates and visiting professors from Africa, Central and South America, Papua New Guinea, China, Nepal, Peru and the Middle East. These efforts have enabled dynamic and broad perspectives in our field, relating to biodiversity conservation, capacity building, economic development in low/middle income nations, and the key future role for natural products in drug discovery/development relevant to many disease areas.
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Adrover-Castellano ML, Schmidt JJ, Glasser CA, Qu F, Sherman DH. ChemRxiv,PreprintDirected Evolution of a Modular Polyketide Synthase Thioesterase for Generation of a Hybrid Macrocyclic Ring System
DOI:10.26434/chemrxiv-2024-02cj6 -
Hohlman RM, Keramati NR, Sherman DH. Advanced Synthesis and Catalysis, 2023 Dec 19; 365 (24): 4520 - 4526.Journal ArticleCooperative Biocatalysis Enables Assembly of a Prenylated Indole Alkaloid
DOI:10.1002/adsc.202300980 -
McCullough TM, Dhar A, Akey DL, Konwerski JR, Sherman DH, Smith JL. Structure, 2023 Sep 7; 31 (9): 1109 - 1120.e3.Journal ArticleStructure of a modular polyketide synthase reducing region.
DOI:10.1016/j.str.2023.05.019 PMID: 37348494 -
Okiye MEK, Velez M, Sugai J, Kinney J, Giannobile W, Tripathi A, Sherman D. 2023 bioRxiv,PreprintInvestigating Metabolic Trends in the Oral Cavity to Identify Novel Metabolites
DOI:10.1101/2023.06.26.546600 -
Shende VV, Harris NR, Sanders JN, Newmister SA, Khatri Y, Movassaghi M, Houk KN, Sherman DH. Angew Chem Int Ed Engl, 2023 May 8; 62 (20): e202210254Journal ArticleMolecular Dynamics Simulations Guide Chimeragenesis and Engineered Control of Chemoselectivity in Diketopiperazine Dimerases.
DOI:10.1002/anie.202210254 PMID: 36610039 -
Shende VV, Harris NR, Sanders JN, Newmister SA, Khatri Y, Movassaghi M, Houk KN, Sherman DH. Angewandte Chemie, 2023 May 8; 135 (20):Journal ArticleMolecular Dynamics Simulations Guide Chimeragenesis and Engineered Control of Chemoselectivity in Diketopiperazine Dimerases
DOI:10.1002/ange.202210254 -
Yancey CE, Yu F, Tripathi A, Sherman DH, Dick GJ. Appl Environ Microbiol, 2023 May 31; 89 (5): e0209222Journal ArticleExpression of Microcystis Biosynthetic Gene Clusters in Natural Populations Suggests Temporally Dynamic Synthesis of Novel and Known Secondary Metabolites in Western Lake Erie.
DOI:10.1128/aem.02092-22 PMID: 37070981 -
Liu Z, Rivera S, Newmister SA, Sanders JN, Nie Q, Liu S, Zhao F, Ferrara JD, Shih H-W, Patil S, Xu W, Miller MD, Phillips GN, Houk KN, Sherman DH, Gao X. Nat Chem, 2023 Apr; 15 (4): 526 - 534.Journal ArticleAn NmrA-like enzyme-catalysed redox-mediated Diels-Alder cycloaddition with anti-selectivity.
DOI:10.1038/s41557-022-01117-6 PMID: 36635598