Control of methionine biosynthesis in Escherichia coli by proteolysis

Most bacterial proteins are stable, with half-lives considerably longer tha n the generation time. In Escherichia coli, the few exceptions are unstable regulatory proteins. The results presented here indicate that the first en zyme in methionine biosynthesis - homoserine trans-succinylase (HTS) - is u nstable and subject to energy-dependent proteolysis. The enzyme is stable i n triple mutants defective in Lon-, HsIVU- and ClpP-dependent proteases. Th e instability of the protein is determined by the aminoterminal part of the protein, and its removal or substitution by the M-terminal part of beta-ga lactosidase confers stability. The effect of the amino-terminal segment is not caused by the N-end rule, as substitution of the first amino acid does not affect the stability of the protein. HTS is the first biosynthetic E. c oli enzyme shown to have a short half-life and may represent a group of bio synthetic enzymes whose expression is controlled by proteolysis. Alternativ ely, the proteolytic processing of HTS may be unique to this enzyme and cou ld reflect its central role in regulating bacterial growth, especially at e levated temperatures.