| Abstract: | The Enzymatic Synthesis of Holotranscarboxylase from Apotranscarboxylase and (+)-Biotin. I. Purification of the Apoenzyme and Synthetase; Characteristics of the Reaction(Lane, M. D., Young, D. L., and Lynen, F. (1964)J. Biol. Chem.239, 2858–2864)Feodor Felix Konrad Lynen (1911–1979) was born in Munich, Germany. He was undecided about his career during his early education and even considered becoming a ski instructor. Ultimately, he enrolled in the Department of Chemistry at the University of Munich where he studied with Nobel laureate Heinrich Wieland and received his doctorate degree in 1937. Three months later, he married Wieland''s daughter, Eva.Open in a separate windowFeodor LynenAfter graduating, Lynen remained at Munich University as a postdoctoral fellow. He was appointed lecturer in 1942 and assistant professor in 1947. When World War II broke out, Lynen was exempt from military service because of a knee injury resulting from a ski accident in 1932. However, the war made it difficult to continue to do research in Munich, and Lynen moved his laboratory to the small village of Schondorf on the Ammersee. This was lucky because in 1945 Munich University''s Department of Chemistry was destroyed. Lynen continued his work at various laboratory facilities and eventually returned to the rebuilt Department of Chemistry in 1949.During the 1940s, Lynen began studying the biosynthesis of sterols and lipids. He eventually initiated a collaboration with Konrad Bloch, whose cholesterol research was featured in a previous Journal of Biological Chemistry (JBC) Classic (1). Working together, Bloch and Lynen were able to elucidate the steps in the biosynthesis of cholesterol. An especially significant finding made by Lynen was that acetyl coenzyme A (previously discovered by JBC Classic author Fritz Lipmann (2)) was essential for the first step of cholesterol biosynthesis. Lynen later determined the structure of acetyl-CoA. This work on cholesterol resulted in Bloch and Lynen being awarded the 1964 Nobel Prize in Physiology or Medicine.In 1953, Lynen was made full professor at the University of Munich. A year later, he was named director of the newly established Max Planck Institute for Cell Chemistry. He continued to work on fats but also turned his focus to biotin-dependent enzymes. In 1962, he was joined by JBC Classic author M. Daniel Lane (3), who had come to Munich to work with Lynen on a sabbatical leave. Lane was studying the biotin-dependent propionyl-CoA carboxylase and had previously determined that its biotin prosthetic group was linked to the enzyme through an amide linkage to a lysyl ?-amino group.Before leaving for Munich, Lane developed an apoenzyme system with which to investigate the mechanism by which biotin became attached to propionyl-CoA carboxylase. This system made use of Propionibacterium shermanii, which expressed huge amounts of methylmalonyl-CoA:pyruvate transcarboxylase, another biotin-dependent enzyme. The organism also had an absolute requirement for biotin in its growth medium and produced large amounts of the apotranscarboxylase when grown at very low levels of biotin.As reported in the JBC Classic reprinted here, Lane and Lynen were able to resolve and purify both the apotranscarboxylase and the synthetase that catalyzed biotin loading onto the apoenzyme. Dave Young, a postdoctoral fellow who had recently completed his medical training at Duke University, collaborated with them on these studies. In a second paper reprinted in the Lane Classic (4), Lane and Lynen showed that the synthetase catalyzed a two-step reaction. The first step involved the ATP-dependent formation of biotinyl-5′-AMP and pyrophosphate after which the biotinyl group was transferred from the AMP derivative to the appropriate lysyl ?-amino group of the apotranscarboxylase. Lane and Lynen also showed that the covalently bound biotinyl prosthetic group, like free biotin, was carboxylated on the 1′-N position (5).In 1972, Lynen moved to the recently founded Max Planck Institute for Biochemistry. Between 1974 and 1976, he was acting director of the Institute while continuing to oversee a lab at the University of Munich. He remained at the Institute until his death in 1979.In addition to the Nobel Prize, Lynen received many honors and awards. These include the Neuberg Medal of the American Society of European Chemists and Pharmacists (1954), the Liebig Commemorative Medal of the Gesellschaft Deutscher Chemiker (1955), the Carus Medal of the Deutsche Akademie der Naturforscher Leopoldina (1961), and the Otto Warburg Medal of the Gesellschaft für Physiologische Chemie (1963). |
