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.

背景：丰富和可再生的生物材料是可持续生产包括天然产品（例如药品和营养品）在内的各种化学药品的理想基础。几十年来，研究人员一直专注于如何改造微生物并开发有效的发酵过程以从生物材料中过量生产这些分子。尽管实验室取得了许多成就，但将其中一些转化为成功的工业应用仍然是一个挑战。

结果：在这里，我们回顾了天然产物生产中代谢工程的策略和应用的最新进展。模块化工程方法（例如多维启发式过程）显着提高了优化长而复杂的生物合成途径的效率。动态途径调节可实现自主调节，并可重新定向代谢碳通量，以避免有毒中间代谢物的积累。微生物共培养通过引入不同物种的竞争或合作来增强天然产物的鉴定和生产过剩。外排工程可用于降低产品毒性或克服储存限制，从而提高产品效价和生产率。

结论：毫无争议，许多创新方法和策略的发展正在逐步促进这种从实验室到天然产物生物合成工业的转变。有时，有必要结合两种或多种策略来获得累加或协同效益。因此，我们预见了可再生生物材料微生物中药物和营养品的生物合成的光明前景。