Starter unit choice determines the production of two tetraene macrolides, rimocidin and CE-108, in Streptomyces diastaticus var. 108

Streptomyces diastaticus var. 108, a newly isolated strain, produces two closely related tetraene macrolides (rimocidin and CE-108) as well as oxytetracycline. A region of 19,065 base pairs of DNA from the S. diastaticus var. 108 genome was isolated, sequenced, and characterized. Ten complete genes and one truncated ORF were located. Disruption of these genes proved that this genomic region is part of the biosynthetic cluster for the two tetraenes. The choice of starter units by the loading module and the in vivo availability of the starter metabolites are crucial for the final ratio of the two macrolides. A second type I PKS, unrelated to tetraene biosynthesis, was also identified; disruption of these genes suggests that they would code for enzymes involved in the biosynthesis of a polyketide that might compete metabolically with rimocidin production.