Single cell genomics: A new engine for natural product discovery

Over 99% of microbial diversity on our planet has resisted cultivation, hindering their exploration for biotechnological applications. The community-level omics techniques have led to an explosive, cultivation-independent discovery of microbial genes but often failed to provide information about linkages among genes in biochemical pathways and organisms. The recent emergence of single cell genomics (SCG) has bridged this knowledge gap, enabling routine, high-throughput recovery of genomic information from virtually any member of a microbial community, independent of cell’s cultivability, community’s complexity and the number of DNA molecules in a cell. This offers a new, powerful engine for natural product discovery from the microbial “uncultured majority”. Complex metabolic pathways can be reconstructed from a single, uncultured cell, facilitating the compatibility of the discovered genes with each other and with their expression systems. Genomic information obtained through SCG also facilitates the cultivation of previously uncultured microorganisms of interest. The integration of SCG-based biochemical pathway discovery with synthetic biology and high-throughput cultivation holds an enormous potential for the discovery of novel natural products, bioremediation and environmentally responsible energy solutions.