No abstract

Ribosomally synthesized and post-translationally modified peptides, or RiPPs, which have mainly isolated from microbes as well as plants and animals, are an ever-expanding group of peptidic natural products with diverse chemical structures and biological activities. They have emerged as a major category of secondary metabolites partly due to a myriad of microbial genome sequencing endeavors and the availability of genome mining software in the past two decades. Heterologous expression of RiPP gene clusters mined from microbial genomes, which are often silent in native producers, in surrogate hosts such as Escherichia coli and Streptomyces strains can be an effective way to elucidate encoded peptides and produce novel derivatives. Emerging strategies have been developed to facilitate the success of the heterologous expression by targeting multiple synthetic biology levels, including individual proteins, pathways, metabolic flux and hosts. This review describes recent advances in heterologous production of RiPPs, mainly from microbes, with a focus on E. coli and Streptomyces strains as the surrogate hosts.

Cyanobacteria produce a plethora of compounds with unique chemical structures and diverse biological activities. Importantly, the increasing availability of cyanobacterial genome sequences and the rapid development of bioinformatics tools have unraveled the tremendous potential of cyanobacteria in producing new natural products. However, the discovery of these compounds based on cyanobacterial genomes has progressed slowly as the majority of their corresponding biosynthetic gene clusters (BGCs) are silent. In addition, cyanobacterial strains are often slow-growing, difficult for genetic engineering, or cannot be cultivated yet, limiting the use of host genetic engineering approaches for discovery. On the other hand, genetically tractable hosts such as Escherichia coli, Actinobacteria, and yeast have been developed for the heterologous expression of cyanobacterial BGCs. More recently, there has been increased interests in developing model cyanobacterial strains as heterologous production platforms. Herein, we present recent advances in the heterologous production of cyanobacterial compounds in both cyanobacterial and non-cyanobacterial hosts. Emerging strategies for BGC assembly, host engineering, and optimization of BGC expression are included for fostering the broader applications of synthetic biology tools in the discovery of new cyanobacterial natural products.