FIG 1.

Genomic, genetic, and synthetic biology approaches toward natural product drug discovery. (a) Exploration of bacteria from understudied environments and taxa follows the hypothesis that different selective pressures may lead to the evolution of distinct chemistry. Genomes are sequenced and biosynthetic gene clusters (BGCs) are identified using bioinformatic tools. (b) BGCs of interest are selected. Heterologous expression in suitable hosts can be used to streamline natural product discovery. Genome editing of native producers offers an alternative approach to aid discovery and to study gene and BGC function. (c) Pathway modification via BGC reprogramming contributes to structure diversification of natural products.