GENETICS OF STREPTOMYCIN PRODUCTION IN STREPTOMYCES-GRISEUS - MOLECULAR-STRUCTURE AND PUTATIVE FUNCTION OF GENES STRELMB2N

The nucleotide sequence of a 5.1 kb fragment from the streptomycin biosynthetic gene cluster from Streptomyces griseus revealed the presence of five open reading frames which form part of two convergently oriented transcription units strDEL and strNB2M. The coding capacity for polypeptide products was calculated to be 35.7 kDa (StrE), 32.2 kDa (StrL), 35.6 kDa (StrN), 38.2 kDa (StrB2), and 21.9 kDa (StrM), respectively. Various observations suggested that the gene products StrD (dTDP-glucose synthase), StrE (dTDP-glucose dehydratase), StrM (dTDP-4-keto-6-deoxyglucose 3,5-epimerase), and StrL (dTDP-dihydrostreptose synthase) are involved in biosynthesis of the streptose moiety of streptomycin. StrE and StrL are significantly similar in primary structure to each other and to other oxidoreductases (epimerases) involved in hexose metabolism. Genes for dTDP-glucose synthase and dehydratase occur in other gene clusters for antibiotic production. Therefore, the strD and strE genes could serve as universal probes indicative of the presence of biosynthetic capacity for 6-deoxyhexose moieties. The StrB2 protein showed 69% amino acid identity to the first-step amidinotransferase StrB1. The presence of both strB genes appears to be the result of a gene duplication event. The gene product StrN contains sequence motifs also conserved in the putative catalytic and/or substrate recognition domains of aminoglycoside phosphotransferases and eucaryotic protein kinases. The possible role of a TTA codon, located near the start of the strN reading frame, in regulation of the str cluster is discussed.