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.