The polyamines putrescine, spermidine, and spermine are major polybasic compounds in all living cells. Research indicates that these amines are important for many systems related to growth and differentiation. We are interested in their physiologic functions, mechanisms of polyamine synthesis, regulation of their biosynthesis and degradation, and how they act in vivo. For this purpose, we have constructed null mutants in each of the biosynthetic steps in both Escherichia coli and in Saccharomyces cerevisiae. These mutants cannot make these amines; hence they are very useful tools to study the physiological effects due to their deprivation.
Our research has focused on extending our studies on the biochemistry, regulation, and genetics of these amines and of the biosynthetic enzymes in S. cerevisiae and E. coli. Our work has demonstrated that the polyamines are required for growth of the organisms, their sporulation, maintenance of the killer dsRNA virus, protection against oxidative damage, protection against elevated temperatures, fidelity of protein biosynthesis, and for the maintenance of mitochondria. We have constructed clones that overproduce the various enzymes and have studied the sequence and structural characteristics of these enzymes. Our research has concentrated on the structure and regulation of ornithine decarboxylase, spermidine synthase, spermine synthase, and S-adenosylmethionine decarboxylase.
Most recently we have been studying the effect of polyamines in stimulating the level of the σ38 subunit (RpoS) of Escherichia coli RNA Polymerase, resulting in the induction of the glutamate decarboxylase-dependent acid response system.
The physiologic function of these amines in bacteria, plants, and eukaryotes requires further study. This is particularly true for mammalian cells, including cancer cells. Eventually, we should consider studies on analogs with therapeutic importance.