Recent advances in heterologous expression of natural product biosynthetic gene clusters in Streptomyces hosts

The heterologous expression of natural product biosynthetic gene clusters (BGCs) has traditionally been used as a genetic platform to link various natural product chemotypes to their corresponding genotypes. In recent years, heterologous expression has played an increasing role in natural products research with the advances in sequencing technologies and bioinformatics tools that allow for the rapid and systematic identification of known and cryptic BGCs from a large number of microbial genome sequences. The advances in synthetic biology have also facilitated the process of heterologous expression by providing tools for rapid cloning and engineering of BGCs to improve production yield or to activate silent BGCs. This paper summarizes the recent progress in the cloning and engineering of natural product BGCs and highlights recent examples of the heterologous expression of both known and cryptic BGCs in Streptomyces hosts, which will continue to play a pivotal role in genomics-driven natural product research.

Automated summary

Heterologous expression is a key platform for linking natural product chemotypes to their genotypes. Advances in sequencing and bioinformatics have enabled rapid identification of known and cryptic BGCs from microbial genomes. Synthetic biology tools have facilitated the cloning and engineering of BGCs to enhance production yield, activating silent BGCs. Heterologous expression in Streptomyces hosts will continue to play a vital role in genomics-driven natural product research.