CCE - Roberts Lecture
Squire J. Booker is an Evan Pugh Professor of Chemistry and of Biochemistry and Molecular Biology at The Pennsylvania State University and holds the Eberly Family Distinguished Chair in Science. He is also an Investigator of the Howard Hughes Medical Institute. Booker received a BA degree with a concentration in Chemistry from Austin College (Sherman, Texas) in 1987. He earned his Ph.D. degree from the Massachusetts Institute of Technology under Professor JoAnne Stubbe (1994) and was supported by NSF–NATO and NIH Fellowships for postdoctoral studies in the laboratories of Dr. Daniel Mansuy (Université René Descartes, Paris, France) and Professor Perry Frey (Institute for Enzyme Research, University of Wisconsin–Madison), respectively. In 1999 he moved to The Pennsylvania State University as an independent investigator. Booker’s research concerns novel mechanisms and pathways for the biosynthesis of various natural products and cellular metabolites, focusing on enzymes that use S-adenosylmethionine and iron-sulfur clusters to catalyze reactions via radical mechanisms. Currently, he is an Associate Editor for the ACS journal Biochemistry and Deputy Editor for ACS Bio & Med Chem Gold.
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.