Recent advances in the direct cloning of large natural product biosynthetic gene clusters.

Large-scale genome-mining analyses have revealed that microbes potentially harbor a huge reservoir of uncharacterized natural product (NP) biosynthetic gene clusters (), and this has spurred a renaissance of novel drug discovery. However, the majority of these are often poorly or not at all expressed in their native hosts under laboratory conditions, and thus are regarded as silent/orphan . Currently, connecting silent to their corresponding NPs quickly and on a large scale is particularly challenging because of the lack of universal strategies and enabling technologies.