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monod-Nobel lecture

monod-Nobel lecture - JA C Q U E S M ONOD From enzymatic...

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J A C Q U E S M O N O D From enzymatic adaptation to allosteric transitions Nobel Lecture, December 11, 1965 One day, almost exactly 25 years ago - it was at the beginning of the bleak winter of 1940 - I entered André Lwoff’s office at the Pasteur Institute. I want- ed to discuss with him some of the rather surprising observations I had recently made. I was working then at the old Sorbonne, in an ancient laboratory that open- ed on a gallery full of stuffed monkeys. Demobilized in August in the Free Zone after the disaster of 1940, I had succeeded in locating my family living in the Northern Zone and had resumed my work with desperate eagerness. I interrupted work from time to time only to help circulate the first clandestine tracts. I wanted to complete as quickly as possible my doctoral dissertation, which, under the strongly biometric influence of Georges Teissier, I had de- voted to the study of the kinetics of bacterial growth. Having determined the constants of growth in the presence of different carbohydrates, it occurred to me that it would be interesting to determine the same constants in paired mixtures of carbohydrates. From the first experiment on, I noticed that, whereas the growth was kinetically normal in the presence of certain mixtures (that is, it exhibited a single exponential phase), two complete growth cycles could be observed in other carbohydrate mixtures, these cycles consisting of two exponential phases separated by a-complete cessation of growth (Fig.1). Lwoff, after considering this strange result for a moment, said to me, "That could have something to do with enzyme adaptation." "Enzyme adaptation? Never heard of it!" I said. Lwoff’s only reply was to give me a copy of the then recent work of Mar- jorie Stephenson, in which a chapter summarized with great insight the still few studies concerning this phenomenon, which had been discovered by Duclaux at the end of the last century. Studied by Dienert and by Went as early as 1901 and then by Euler and Josephson, it was more or less rediscovered by Karström, who should be credited with giving it a name and attracting attention to its existence. Marjorie Stephenson and her students Yudkin and
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E N Z Y M A T I C A D A P T A T I O N A N D A L L O S T E R I C T R A N S I T I O N S 1 8 9 80 Fig.1. Growth of Esherichia coli in the presence of different carbohydrate pairs serving as the only source of carbon in a synthetic medium 50 . Gale had published several papers on this subject before 1940. [See ref. I for a bibliography of papers published prior to 1940] Lwoff’s intuition was correct. The phenomenon of "diauxy" that I had discovered was indeed closely related to enzyme adaptation, as my experi- ments, included in the second part of my doctoral dissertation, soon convinced me. It was actually a case of the "glucose effect" discovered by Dienert as early as 1900, today better known as "catabolic repression" from the studies of Magasanik 2 .
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