Microbial isopenicillin N synthase genes: structure, function, diversity and evolution.
Clinically and economically, penicillins and cephalosporins are the most important class of the beta-lactam antibiotics. They are produced by a wide variety of microorganisms including numerous species of Streptomyces, some unicellular bacteria and several filamentous fungi. A key step common to their biosynthetic pathways is the conversion of a linear, cysteine-containing tripeptide to a bicyclic beta-lactam antibiotic by isopenicillin N synthase. Recent successes in the cloning and expression of isopenicillin N synthase genes now permit production of a plentiful supply of this enzyme, which may be used for structural and mechanistic studies, or for biotechnological applications in the creation of novel beta-lactam compounds from peptide analogues. New ideas concerning the evolution and prevalence of the penicillin and cephalosporin biosynthetic genes have emerged from studies of isopenicillin N synthase genes.
Cohen
G
G
Faculty of Life Sciences, Department of Microbiology, Tel Aviv University, Ramat Aviv, Israel.
Shiffman
D
D
Mevarech
M
M
Aharonowitz
Y
Y
D000595:Amino Acid Sequence; D005075:Biological Evolution; D014644:Genetic Variation; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000235:genetics*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics; D013329:Structure-Activity Relationship
D010088:Oxidoreductases; C038370:isopenicillin N synthetase