With the increasing prevalence of antimicrobial resistance coupled with the dwindling supply of new antibiotics, it is critical that innovative solutions be implemented that would allow rapid discovery of novel compounds from natural sources. Soil microbes are wealthy in genetically-encoded small molecules and have been successful sources of effective antibiotics. Conventional cultivation approaches have been widely used to discover novel environmental bacteria. However, these techniques only lead to rediscoveries because only a fraction of bacteria can be grown under standard conditions. This growth bottleneck greatly diminishes our ability to capture the wealth of chemical diversity found in nature and ultimately impedes NP discovery. To break this bottleneck, we propose a metagenomic-driven pipeline that bypasses the need of cultivation for NP discovery. The vast genetic diversity of soil microbes are fully harnessed and converted to genetic libraries that could be expressed in a heterologous host. A multi-disciplinary approach combining microbiology, genomics and synthetic biology will be employed that would allow efficient discovery of novel biosynthetic genes and bioactive small molecules.