Antitermination control of bacterial antibiotic gene clusters

Our laboratories are investigating the function of post-transcriptional regulation for efficient expression of antibiotic biosynthetic genes. A fundamental problem in molecular biology is how the RNA polymerase complex sustains transcription of very long RNAs, a characteristic of many natural product gene clusters in bacteria. We have uncovered a new element that functions in processive antitermination (PA) of a polyketide biosynthetic gene cluster in Bacillus subtilis. Production of the product, bacillaene, is dependent upon the PA element. A second, similar element was found in a long operon associated with biofilm matrix production in B. subtilis. Remarkably, we find the two elements are interchangeable between pathways. Also, when inserted in the ~26 kb operon of a third, unrelated antibiotic pathway, the elements forcibly promote expression of the downstream genes. These findings suggest that RNA-encoded antitermination elements may significantly increase expression of silent gene clusters for heterologous expression of antibiotic pathways. Synthetic application of these elements would greatly improve access to many new candidate antibiotics and other potential natural products.