Search For Regulatory Logic In De Novo Pyrimidine Biosynthesis In Bacteria

Abstract

The de novo pyrimidine biosynthetic pathway produces the pyrimidine end products uridine-5'-triphosphate (UTP) and cytidine-5’-triphosphate (CTP), which lead to the synthesis of new DNA and RNA for cell growth. Aspartate transcarbamoylase (ATCase, E.C. 2.1.3.2.) catalyzes the first committed step of de novo metabolic flux into pyrimidine biosynthesis and is controlled through feedback inhibition of existing enzyme by CTP and repression of enzyme formation by UTP in E. coli. ATCase is encoded by a single bicistronic operon pyrBI in members of the Enterobacteriaceae; however, allosteric regulation of ATCase varies among classes of enteric bacteria. Some of these variations include activation by the end product CTP. In order to gain insight into this regulatory logic, repression of pyrBI expression has been studied in heterologous gene systems of S. marcescens and P. vulgaris transformed into an E. coli host.