Escherichia coli as a cell factory for heterologous production of nonribosomal peptides and polyketides

Nonribosomal peptides (NRPs) and polyketides (PKs) are two classes of natural products with numerous bioactivities such as antiviral, antimicrobial and anticancer activity. However, pharmaceutical applications of these products are often impeded because many native producers are difficult to cultivate or show a low productivity. Over the last decade, with the development of synthetic biology and metabolic engineering, more and more bioactive natural products including NRPs and PKs have been heterologously produced using easy-to-handle surrogate microbes. In this process, the full biosynthetic pathway for the production of a target compound is first identified and isolated from the native producer, and then reconstituted in a well-characterized and easily culturable heterologous producer like Escherichia coli. Thereafter, the productivity could be rationally improved through multiple strategies from strain to bioprocess optimization. This review summarizes the endeavors and progresses made in the heterologous production of NRPs, PKs and NRP/PK hybrids using E. coli as a robust whole-cell factory in recent years.