Heterologous biosynthesis as a platform for producing new generation natural products

[Display omitted] •Natural products include numerous societally valuable compounds.•Medicinally relevant natural products include many clinical antibiotics.•Escherichia coli is a common heterologous host for natural product biosynthesis.•Other heterologous hosts correlate with different natural product classes.•Heterologous biosynthesis remains a common route to access natural products. Natural products have demonstrated value across numerous application areas, with antibiotics a notable historical example. Native cellular hosts provide an initial option in efforts to harness natural product production. However, various complexities associated with native hosts, including fastidious growth traits and limited molecular biology tools, have prompted an alternative approach termed heterologous biosynthesis that relies upon a surrogate biological system to reconstitute the biosynthetic sequence stemming from transplanted genetic blueprint. In turn, heterologous biosynthesis offers the benefit of enzymatically driven complex natural product formation combined with the prospect of improved compound access via scalable cellular production. In this review, we conduct a literature meta-analysis of heterologous natural product biosynthesis over the period of 2011−2020 with the goal of identifying trends in heterologous natural product host selection, target natural products, and compound-host selection tendencies, with associated commentary on the research directions of heterologous biosynthesis based upon this analysis.