Biotransformation Innovation Platform (BioTrans), Agency for Science, Technology and Research (A*STAR), Singapore.
Curr Med Chem. 2020;27(28):4613-4621. doi: 10.2174/0929867327666200212121047.
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.
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.
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.
丰富且可再生的生物材料是可持续生产各种化学品的理想基质，包括天然产物（例如，药品和营养保健品）。几十年来，研究人员一直致力于如何对微生物进行工程改造，并开发有效的发酵工艺，从生物材料中大量生产这些分子。尽管在实验室取得了许多成果，但要将其中一些转化为成功的工业应用仍然具有挑战性。
在这里，我们回顾了代谢工程在天然产物生产方面的策略和应用的最新进展。模块化工程方法，如多维启发式过程，显著提高了优化长而复杂生物合成途径的效率。动态途径调控实现了自主调整，可以重新引导代谢碳通量，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，促进了天然产物的鉴定和过量生产。外排工程用于降低产物毒性或克服储存限制，从而提高产物的浓度和产率。
毫无疑问，许多创新的方法和策略的发展正在逐渐将天然产物生物合成从实验室推向工业界。有时，需要结合两种或更多策略以获得附加或协同效益。因此，我们预见了从可再生生物材料中利用微生物生产药品和营养保健品的光明前景。
