TRANSLATIONAL AUTOREGULATION OF THE SGM GENE FROM MICROMONOSPORA-ZIONENSIS

The sisomicin-gentamicin resistance methylase gene (sgm) from Micromon ospora zionensis (the producer of antibiotic G-52 [6-N-methyl-sisomici n]) encodes an enzyme that modifies 16S rRNA and thereby confers resis tance to 4,6-disubstituted deoxystreptamine aminoglycosides, Here, we report that this gene is regulated on the translational level. The Esc herichia coil lacZ gene and operon fusion system was used, and it was shown that an extra copy of the sgm gene decreases the activity of the fusion protein, These results suggested that expression of the sgm ge ne is regulated by the translational autorepression because of binding of the methylase to its own mRNA, It was shown by computer analysis t hat the same hexanucleotide (CCGCCC) is present 14 bp before the ribos ome-binding site and in the C-1400 region of 16S rRNA, i.e., the regio n in which most of the aminoglycosides act. A deletion that removes th e hexanucleotide before the gene fusion is not prone to negative autor egulation, This mode of regulation of the sgm gene ensures that enough methylase molecules protect the cell from the action of its own antib iotic, On the other hand, if all of the ribosomes are modified, Sgm me thylase binds to its own mRNA in an autorepressive manner.