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A remarkable reservoir of natural product biosynthetic gene clusters has been uncovered along with the growing number of sequenced microbial genomes.However, many cryptic biosynthetic gene clusters appear to be expressed poorly, or not at all, under laboratory growth conditions and their products are still unknown.A double reporter-guided mutant selection (dRGMS) method was developed wherein reporters were used to facilitate selection of target over-expressed mutants.It was originally applied to awake jadomycin biosynthesis gene cluster in Streptomyces venezuelae ISP5230.