Resistance, regulatory and production genes for the antibiotic methylenomycin are clustered.

Abstract

At least 17 kb of DNA from the large unisolatable Streptomyces coelicolor A3(2) plasmid SCP1 are concerned with methylenomycin biosynthesis. Mutational cloning analysis, using insert‐directed integration of att site deleted phage vectors into an SCP1‐containing host, provided evidence of two large transcription units, of at least 6.6 kb and 9.5 kb. At the leftmost apparent end of the larger (left‐hand) transcription unit is a region apparently involved in negative regulation of methylenomycin biosynthesis: when fragments from this region were used to direct phage integration, marked overproduction of methylenomycin resulted. The methylenomycin resistance determinant is located at the rightmost end of this same transcription unit. Hybridisation analysis with 13 kb of the cloned mmy region showed that it was closely similar to a segment of pSV1, a plasmid that specifies methylenomycin biosynthesis in S. violaceus‐ruber SANK 95570.

A relA/spoT Homologous Gene from Streptomyces coelicolor A3(2) Controls Antibiotic Biosynthetic Genes

“…For the first three compounds, it has been reported that their biosynthesis is controlled by the action of specific regulatory genes located within the particular biosynthetic clusters (4,(7)(8)(9). Such regulatory genes have also been identified in other antibiotic clusters, such as bialaphos (10), streptomycin (11,12), and daunorubicin (13).…”

Characterization of Two Different Types of Resistance Genes Among Producers of Fortimicin-Group Antibiotics

“…Antibiotic biosynthesis genes are generally clustered in limited regions in the genome, and the genes conferring resistance to the organism's own products are usually located in or near the gene clusters (Rhodes et a/., 1984;Ohnuki et al, 1985;Chater & Bruton, 1985;Malpartida & Hopwood, 1986;Murakami et al, 1986;Stanzak et al, 1986;Fishman et al, 1987). These facts seem to suggest a tight genetic linkage between antibiotic biosynthesis genes and the resistance genes during the evolution and the horizontal distribution of antibiotic biosynthesis systems.…”

Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters

“…6 In particular, extensive genetic studies by Hopwood and colleagues 7,8 confirmed that the plasmid SCP1 carries the biosynthetic (mmy) genes for methylenomycin (Figure 1) in S. coelicolor A3(2). Furthermore, the mmy gene cluster was cloned by mutational cloning and analyzed in detail, 9 even though SCP1 itself was still resistant to isolation and its physical identity had not been clarified. The application of pulsed-field gel electrophoresis (PFGE) to Streptomyces DNA changed this situation and revealed that SCP1 is a giant linear plasmid of about 350 kb.…”