CONTROL OF PYRIMIDINE BIOSYNTHESIS IN ESCHERICHIA COLI BY A FEED-BACK MECHANISM

Abstract

The mechanisms by which a cell can control its biosynthetic processes are important from the point of cellular economy, yet they are little understood. It is known that bacteria must have such control systems, since their biochemical processes are so well coordinated, as shown by failure of the cell to accumulate large amounts of metabolites in the medium (1). Several indications of control mechanisms have been found. One type of observation is that addition of a few micrograms per ml. of normal purines (2)) pyrimidines (1)) or amino acids (3,l) to growth media of normal bacteria could result in nearly exclusive incorporation of these materials into cell constituents, in preference to de novo synthesis of the materials by the cell. It has been noticed also that production of intermediates of the above materials can be inhibited by addition of the end-products to cultures of suitable bacterial mutants. Gots and Chu (4) and Love and Gots (5) found that addition of purines to the culture medium of purinerequiring Escherichia coli mutants caused inhibition of formation of two purine precursors, and Brooke et al. (6) showed the inhibition of erotic acid (0A)i formation in the presence of uracil by pyrimidine-requiring Aerobacter aerogenes mutants. Adelberg and Umbarger (7) observed that the presence of the growth factor, valine, inhibited formation in an E. coli mutant of a-ketoisovalerate, a valine precursor, and commented that the unknown mechanism was undoubtedly wide-spread and important to the economy of the cell. Work from this Laboratory indicated that the presence of uracil inhibited formation of pyrimidine intermediates earlier than erotic acid in pyrimidinerequiring E. coli mutants (8). It seemed of interest to determine whether this observation plus the above facts could be the results of normal selfregulatory mechanisms of the cell which allowed formation of no more