September 21, 2023 12:30 pm
September 21, 2023 2:00 pm
A Radical Solution for C(sp3)–C(sp3) Bond Formation during the Biosynthesis of Macrocyclic Membrane Lipids
Evan Pugh University Professor and Eberly Distinguished Chair in Science
Pennsylvania State University
Squire J. Booker is an Evan Pugh Professor of Chemistry and of Biochemistry and Molecular Biology, and the Eberly Family Distinguished Chair in Science at the Pennsylvania State University. He is also an investigator of the Howard Hughes Medical Institute. Booker’s research focuses on the enzymology of natural product biosynthesis, with a particular interest in the methylation or sulfidation of unactivated carbon centers, and the use of S-adenosylmethionine and iron-sulfur clusters in enzyme catalysis. In addition to his scientific endeavors, he is heavily involved in the mentoring of young scientists, and particularly those that come from groups that are historically underrepresented in the sciences. Currently, he is the PI on an NSF award entitled “Interactive Mentoring And Grantsmanship Enhancement,” which seeks to demystify the grant-writing process for early stage investigators.
Archaea synthesize isoprenoid-based ether-linked membrane lipids, which enable them to withstand extreme environmental conditions, such as high temperatures, high salinity, and low or high pH values. In some archaea, such as Methanocaldococcus jannaschii, these lipids are further modified by forming carbon–carbon bonds between the termini of two lipid tails within one glycerophospholipid to generate the macrocyclic archaeol or forming two carbon–carbon bonds between the termini of two lipid tails from two glycerophospholipids to generate the macrocycle glycerol dibiphytanyl glycerol tetraether (GDGT). GDGT contains two 40-carbon lipid chains (biphytanyl chains) that span both leaflets of the membrane, providing enhanced stability to extreme conditions. How these specialized lipids are formed has puzzled scientists for decades. The reaction necessitates coupling two completely inert sp3-hybridized carbon centers, which has not been observed in nature. Here we use X-ray crystallography, high-resolution mass spectrometry, chemical synthesis, and biochemical analyses to show that the gene product of mj0619 from M. jannaschii, which encodes a radical S-adenosylmethionine enzyme, is responsible for biphytanyl chain formation during synthesis of both the macrocyclic archaeol and GDGT membrane lipids.
Eastman Chemical Company is proud to be a long time sponsor of the Carolina Colloquia’s Annual Eastman Lecture as part of our partnership with the Department of Chemistry at UNC. Ten years ago, Eastman opened the Eastman Innovation Center – Chapel Hill to establish a research partnership with the university. Since then, they have sponsored more than 30 projects totaling over $7M. Projects have included fundamental studies, probing the structure-property relationships of Eastman materials and utilizing computational methodology to direct synthetic efforts. In addition, they have been active participants and sponsors of programs like Winspire, Accelerate to Industry and the Eastman Chemical Company Fellowship program for underrepresented graduate students. To learn more about Eastman, visit their website