On Growth Laws, Catabolite Repression, and Metabolic Coordination

Seminar series
Physical Chemistry Seminar
Mon, May 6 4:00pm
2033 Young Hall
Speaker Professor Terry Hwa
University of California, San Diego
Dept. of Physics

Abstract: Carbon catabolite repression (CCR) is one of the most intensively studied systems in molecular biology; yet many mysteries remain, regarding its physiological function and molecular implementation. We investigated these issues using a quantitative physiological approach. Through extensive characterization of the growth and expression of exemplary metabolic genes using a variety of mutants under many combinations of nutrient limitations, we revealed striking linear relations linking the expressions of catabolic genes and the rate of cell growth in E. coli. They can be understood in terms of two powerful constraints governing cell growth and metabolism: the balance of metabolic fluxes which is well known, and the partitioning of the ribosomal load which is not widely appreciated. The results of our study establish that CCR is not about catabolism per se, but about the coordination between catabolism and biosynthesis. Furthermore, we show that this coordination is implemented molecularly by an integral feedback scheme involving metabolic precursors and that it does not require the phosphotransferase system commonly thought to underlie catabolic control in E. coli. These findings demonstrate the power of the “top-down approach”, both in providing predictive understandings of physiological responses and in elucidating key regulatory mechanisms that evaded extensive molecular studies.