CHARACTERIZATION OF A STREPTOMYCES-ANTIBIOTICUS GENE-CLUSTER ENCODINGA GLYCOSYLTRANSFERASE INVOLVED IN OLEANDOMYCIN INACTIVATION

By homology to the mgt gene (encoding a macrolide glycosyltransferase) from Streptomyces lividans, a 3.3-kb DNA fragment from the oleandomyc in producer, Streptomyces antibioticus, was cloned and sequenced. Anal ysis of the sequence revealed the presence of the 3' end of a gene (OR F1) and two complete ORFs (ORF2 and oleD), ali of them translationally coupled. The deduced product of the sequenced region of ORF1 containe d the typical signature of integral membrane proteins responsible for the translocation of substrates across the membrane. The ORF2 product did not show significant similarity with proteins in databases, but co ntains an N-terminus leader peptide region characteristic of secreted proteins, and a lipid attachment site motif characteristic of membrane lipoproteins synthesized with a precursor signal peptide. The oleD pr oduct showed clear similarity with several UDP-glucuronosyl- and UDP-g lycosyl-transferases from different origins and particularly with the mgt gene from S. lividans, and might encode a glycosyltransferase acti vity capable of inactivating macrolides. It is proposed that these thr ee genes could participate in the intracellular glycosylation of olean domycin and its secretion during antibiotic production.