Bowie, James U.

Biochemistry

Bowie James

Biography

Bowie got hooked on proteins at an early age and never looked back. The obsession began as a high school student when he did a research project on blood clotting enzymes with Kenneth G. Mann at the Mayo Clinic in his hometown of Rochester, MN. The research project won him a trip to the International Science and Engineering fair and a Westinghouse Award, experiences that further stimulated his interest in science. He went on to Carleton College, where he got a B. A. degree in Chemistry with Distinction. He did research in carbohydrate chemistry with Gary R. Gray at the University of Minnesota before entering graduate school at M.I.T. There he returned to proteins in the laboratory of Robert T. Sauer, using experimental and computational methods to probe and predict protein structure. After completing his Ph.D. work, he did postdoctoral work with David Eisenberg at UCLA, continuing work on structure prediction and structure determination by x-ray crystallography. He joined the UCLA faculty in 1993 and is now a full professor.

Research Interests

Membrane Protein Folding

Protein folding is a fundamental process of life with important implications throughout biology. Elaborate mechanisms exist to regulate and assist folding. Moreover, tens of thousands of mutations have now been associated with diseases and it is thought that most of these mutations affect protein folding and trafficking rather than function. Consequently, there has been an enormous effort over the years to understand how proteins fold. Essentially all of the effort has been directed at soluble proteins, however, and membrane proteins have been largely shunted aside. The lack of effort has not occurred because membrane proteins are unimportant or uninteresting, but because of the great technical challenges they present. It is a challenge that we must overcome if we ever hope to understand membrane biology and disease mechanisms involving a large fraction of the protein universe. We are working to understand folding mechanisms and to develop techniques to study folding and expand the field.

 

Synthetic Biochemistry for Green Production of Chemicals and Biofuels

Considerable effort is currently directed to engineer micro-organisms to produce useful chemicals. The greatest potential environmental benefit of metabolic engineering would be the production of high volume commodity chemicals, such as biofuels. Yet the high yields required for the economic viability of low-value chemicals are particularly hard to achieve in microbes due to the myriad competing biochemical pathways. We are developing an alternative approach, which we call synthetic biochemistry. Synthetic biochemistry throws away the cells and builds biochemical pathways in reaction vessels using complex mixtures of isolated enzymes. As the only pathway in the vessel is the desired transformation, yields can approach 100%. The challenge for synthetic biochemistry is to replace the complex regulatory systems that exist in cells in a simplified form. We are designing and testing various ideas for building highly robust systems that can operate continuously for long periods of time.

 

SAM Domains

SAM domains are one of the most common protein modules found in eukaryotic cells. We discovered that many SAM domains can form polymers, establishing the existence of a new biological polymer. We explore how SAM domains are involved in building large biological structures and how SAM domain mutations lead to disease.

 

Honors & Awards

  • 2020 Stein&Moore Award of the Protein Society
  • 2019 Paul M. Horowitz Memorial Lecturer, UT San Antonio
  • 2018 Fellow of the Biophysical Society Award
  • 2018 Choh Hao Li Memorial Lecturer, Academia Sinica
  • 2018 UCLA Postdoctoral Society Postdoc Mentoring Award Finalist
  • 2017 Biophysical Society Anatrace Membrane Protein Award
  • 2016 Higgs Lecture at Kings College, London
  • 2012 Elected President of the Protein Society for 2013-14
  • 2012 UCLA Society of Postdoctoral Scholars Postdoctoral Mentoring Award
  • 2009 Dreyfus Foundation Postdoc Prog in Envir. Chem. Mentor
  • 2008 Re-elected to Protein Society Executive Council
  • 2008 Elected Fellow of AAAS
  • 2007 Elected Chair, 2009&11 Gordon Conference on Proteins
  • 2006 Elected to the Protein Society Executive Council
  • 2004 Elected Chair, 2006&8 FASEB Conference on Mol. Biophys. of Cell. Membranes
  • 2001 Leukemia and Lymphoma Society Scholar
  • 1998 McCoy Award in Chemistry
  • 1994 NSF National Young Investigator
  • 1994 Pew Scholar
  • 1992 American Cancer Society Postdoctoral Fellowship
  • 1989 Life Sciences Research Foundation Postdoctoral Fellowship
  • 1981 Distinction in Chemistry, Carleton College
  • 1981 Elected to Phi Beta Kappa

Representative Publications

Below is the list of the most recent publications.  For the full list, please visit here.

  • Aoki M, Vinokur J, Motoyama K, Ishikawa R, Collazo M, Cascio D, Sawaya MR, Ito T, Bowie JU, Hemmi H. Crystal structure of mevalonate 3,5-bisphosphate decarboxylase reveals insight into the evolution of decarboxylases in the mevalonate metabolic pathways. J Biol Chem. 298(7):102111 (2022)
  • Liu H, Arbing MA, Bowie JU. Expanding the use of ethanol as a feedstock for cell-free synthetic biochemistry by implementing acetyl-CoA and ATP generating pathways. Sci Rep. 12(1):7700 (2022)
  • Corin K, Bowie JU. How physical forces drive the process of helical membrane protein folding. EMBO Rep. 23(3):e53025 (2022)
  • Liu H, Bowie JU. Cell-free synthetic biochemistry upgrading of ethanol to 1,3 butanediol. Sci Rep. 11(1):9449. (2021)
  • Corin K, Bowie JU. How bilayer properties influence membrane protein folding. Protein Sci. 29(12):2348-2362 (2020)
  • Sherkhanov S, Korman TP, Chan S, Faham S, Liu H, Sawaya MR, Hsu W-T, Cheng T, Bowie JU, Isobutanol production freed from biological limits using synthetic biochemistry, Nature Comm., 10.1038/s41467-020-18124-1 (2020)
  • Valliere MA, Korman TP, Arbing MA, Bowie JU, A bio-inspired cell free system for cannabinoid production from inexpensive inputs, Nature Chem. Biol., 10.1038/s41589-020-0631-9 (2020)
  • Bowie JU, Sherkhanov S, Korman TP, Valliere MA, Opgenorth P, Liu H, Synthetic Biochemistry:  The bio-inspired cell free approach to commodity chemical production, Trends in Biotech., 38(7):766-778 (2020)
  • Choi HK, Min D, Kang H, Shon MJ, Rah SH, Kim HC, Jeong H, Choi HJ, Bowie JU, Yoon TY., Watching helical membrane proteins fold reveals a common N-to-C-terminal folding pathway. Science. 2019 Nov 29;366(6469):1150-1156
  • Valliere MA, Korman TP, Woodall NB, Khitrov GA, Taylor RE, Baker D, Bowie JU, A cell-free platform for the prenylation of natural products and application to cannabinoid production, Nature Comm., 10(1):565 (2019)