Comparative transcriptomics as a guide to natural product discovery and biosynthetic gene cluster functionality
Significance Genomics has revealed that even well-studied bacteria maintain many more biosynthetic gene clusters (BGCs) predicted to encode specialized metabolites than expected based on product discovery. These orphan BGCs are often assumed to be transcriptionally silent. Here, we show that a majority of the 46 BGCs observed in four strains of the marine actinomycete Salinispora are transcribed at levels that should facilitate product detection. In five cases, similar BGCs were differentially expressed among strains, suggesting that simple presence or absence analyses are not good predictors of metabolic output. Highly expressed BGCs were bioinformatically linked to their products, including a series of salinipostins not previously reported from Salinispora pacifica . Subsequent genetic experiments established a formal link between salinipostins and their cognate BGC.