Free Radical Biology & Medicine. Vol. 5. pp. 377-385, 1988 0891-5849/88 $3.00 + .00 Printedin the USA.All rightsreserved. © 1988Pergamon Pressplc Review Article BIOSYNTHESIS AND REGULATION OF SUPEROXIDE DISMUTASES HOSNI M. HASSAN Departments of Food Science and Microbiology, North Carolina State University, Raleigh, NC 27695-7624, U.S.A. Abstract--The past two decades have witnessed an explosion in our understanding of oxygen toxicity. The discovery of superoxide dismutases (SODs) (EC. 1.15.1.1), which specifically catalyze the dismutation of super- oxide radicals (02-) to hydrogen peroxide (H202) and oxygen, has indicated that O2- is a normal and common byproduct of oxygen metabolism. There is an increasing evidence to support the conclusion that superoxide radicals play a major role in cellular injury, mutagenesis, and many diseases. In all cases SODs have been shown to protect the cells against these deleterious effects. Recent advances in molecular biology and the isolation of different SOD genes and SOD c-DNAs have been useful in. proving beyond doubt the physiological function of the enzyme. The biosynthesis of SODs, in most biological systems, is under rigorous controls. In general, exposure to increased pO2, increased intracellular fluxes of O2-, metal ions perturbation, and exposures to several environmental oxidants have been shown to influence the rate of SOD synthesis in both prokaryotic and eukaryotic organisms. Recent developments in the mechanism of regulation of the manganese-containing superoxide dismutase of Escherichia coli will certainly open new research avenues to better understand the regulation of SODs in other organisms. Keywords--pO2, O2-, Growth rate, Metal depletion/repletion, Anaerobic synthesis of MnSOD, Redox-sensitive repressor, Autogenous regulation, Environmental stresses, Free radical INTRODUCTION Superoxide dismutases (SODs) (EC. 1.15.1.1) are me- talloenzymes that are widely distributed among oxy- gen-consuming organisms, aerotolerant anaerobes, and some obligate anaerobes. They are essential for the defense against oxygen toxicity, which is mediated by the partially reduced oxygen intermediates (O2-, HzO2, Paper number 11454 of the Journal Series of the North Carolina Agricultural Research Service, Raleigh, NC 27695. The use of trade names in this publication does not imply endorsement by the North Carolina Agricultural Research Service of the products named, nor criticism of similar ones not mentioned. Hosni M. Hassan was born in 1937 in Alexandria, Egypt. He received his B. Sc (Agriculture) in 1959 from the University of Ain- Shams, Cairo; and his Ph.D. (Microbiology)in 1967, from the Uni- versity of California at Davis (UCD). He was an assistant professor of microbiology and biochemistry at Cairo High Polytechnical In- stitute, then at the University of Alexandria. In 1972, he moved back to North America. He was a visiting professor at the Macdonald College of McGill University, Assistant Microbiologist at the Uni- versity of Maine, and a Research Associate in Fridovich's laboratory at Duke University. Currently he is a Professor of Food Science, Microbiologyand Toxicologyat N.C. State University. Dr. Hassan's research interests are in the areas of Microbial Physiology and En- zymology. During the past 13 years, he has been interested in oxygen toxicity, biological roles of antioxidant enzymes, and the biosyn- thesis and regulation of superoxide dismutases in microorganisms. Dr. Hassan is an American Fulbright Senior Research-Scholar in France. 1987-1988. He enjoys travel, photography, walking, and reading. 377 and .OH) generated during the normal biological re- duction of dioxygen. SODs are unique in that their substrate is a free radical and that they catalyze the dismutation of O2- to H20: and 02 at a very fast rate, 2 x 109 M-Is -1. SODs, isolated from a wide range of organisms, fall into three types depending on the metal found in their active center. McCord and Fridovich ~were the first to describe the superoxide-dismuting ability of a green copper-containing protein that was isolated some 30 years earlier,: and thought to be a copper storage pro- tein. This enzyme is now known to contain both copper and zinc (CuZnSOD) where the zinc plays a structural role. The other two types of SODs were soon discov- ered: one contains manganese (MnSOD)) and the sec- ond contains iron (FeSOD)? The distribution of these three forms of SODs is distinctly different, and may provide an interesting evolutionary scheme. The CuZnSODs are typically found in the cytosol of eu- karyotes, while FeSODs are found in prokaryotes. On the other hand, MnSODs are found in prokaryotes and in mitochondria. There are, however, some exceptions to this simplified evolutionary scheme (For a recent complete account, see Bannister et al)). Amino acid sequence data show that the three types of SODs fall into two distinct phylogenetic families, the CuZnSOD