Fig. 1. Production of bacterial natural products using native and heterologous host systems.

Native producers encode all the necessary genes in a biosynthetic gene cluster (BGC) for the biosynthesis of a target natural product. The BGC can be cloned from the native host and refactored for expression in a heterologous production host. In the case of heterologous production, biosynthetic genes can also be obtained through de novo gene synthesis or cloned from environmental DNA. Additionally, the choice of hosts and pathway engineering strategies are critical in ensuring production of the desired metabolite in heterologous systems. Both native and heterologous production hosts usually produce very low amounts of the natural compound and host engineering will be needed to improve production titers and productivity to obtain sufficient quantities for product purification/identification or for commercial production. Engineered hosts with improved production properties can be used as heterologous production hosts. Further bioprocess optimization can be performed after host engineering.