Abstract

Backgrounds: Abundant and renewable biomaterials serve as ideal substrates for the sustainable production of various chemicals, including natural products (e.g., pharmaceuticals and nutraceuticals). For decades, researchers have been focusing on how to engineer microorganisms and developing effective fermentation processes to overproduce these molecules from biomaterials. Despite many laboratory achievements, it remains a challenge to transform some of these into successful industrial applications.

Results: Here, we review recent progress in strategies and applications in metabolic engineering for the production of natural products. Modular engineering methods, such as a multidimensional heuristic process markedly improve efficiencies in the optimization of long and complex biosynthetic pathways. Dynamic pathway regulation realizes autonomous adjustment and can redirect metabolic carbon fluxes to avoid the accumulation of toxic intermediate metabolites. Microbial co-cultivation bolsters the identification and overproduction of natural products by introducing competition or cooperation of different species. Efflux engineering is applied to reduce product toxicity or to overcome storage limitation and thus improves product titers and productivities.

Conclusion: Without dispute, many of the innovative methods and strategies developed are gradually catalyzing this transformation from the laboratory into the industry in the biosynthesis of natural products. Sometimes, it is necessary to combine two or more strategies to acquire additive or synergistic benefits. As such, we foresee a bright future of the biosynthesis of pharmaceuticals and nutraceuticals in microbes from renewable biomaterials.

Keywords: Natural products, secondary metabolites, metabolic engineering, synthetic biology, modular engineering, dynamic regulation, microbial co-cultivation, efflux engineering.