Conjugation mediates large-scale chromosomal transfer inStreptomycesdriving diversification of antibiotic biosynthetic gene clusters

Streptomyces are ubiquitous soil dwelling bacteria of special importance as a source of metabolites used in human and veterinary medicine, agronomy and industry. Conjugation is the main mechanism of Streptomyces Horizontal Gene Transfer, and this process has long been known to be accompanied by mobilization of chromosomal DNA. However, the magnitude of DNA transfer, or the localization of acquired DNA across their linear chromosome, has remained undetermined. We here show that conjugative crossings in sympatric strains of Streptomyces result in the large-scale, genome-wide distributed replacement of up to one third of the recipient chromosome, a phenomenon for which we propose the name ‘ Streptomyces Chromosomal Transfer’ (SCT). Such chromosome blending results in the acquisition, loss and hybridization of Specialized Metabolite Biosynthetic Gene Clusters, leading to a novel metabolic arsenal in exconjugant offspring. Harnessing conjugation-mediated SMBGC diversification holds great promise in the discovery of new bioactive compounds including antibiotics.