Park Dongwon, Swayambhu Girish, Lyga Thomas, Pfeifer Blaine A
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY, USA.
Synth Syst Biotechnol. 2021 Jan 5;6(1):1-11. doi: 10.1016/j.synbio.2020.12.001. eCollection 2021 Mar.
Natural products have had a major impact upon quality of life, with antibiotics as a classic example of having a transformative impact upon human health. In this contribution, we will highlight both historic and emerging methods of natural product bio-manufacturing. Traditional methods of natural product production relied upon native cellular host systems. In this context, pragmatic and effective methodologies were established to enable widespread access to natural products. In reviewing such strategies, we will also highlight the development of heterologous natural product biosynthesis, which relies instead on a surrogate host system theoretically capable of advanced production potential. In comparing native and heterologous systems, we will comment on the base organisms used for natural product biosynthesis and how the properties of such cellular hosts dictate scaled engineering practices to facilitate compound distribution. In concluding the article, we will examine novel efforts in production practices that entirely eliminate the constraints of cellular production hosts. That is, cell free production efforts will be introduced and reviewed for the purpose of complex natural product biosynthesis. Included in this final analysis will be research efforts made on our part to test the cell free biosynthesis of the complex polyketide antibiotic natural product erythromycin.
天然产物对生活质量产生了重大影响，抗生素就是对人类健康产生变革性影响的一个典型例子。在本论文中，我们将重点介绍天然产物生物制造的历史方法和新兴方法。传统的天然产物生产方法依赖于天然细胞宿主系统。在此背景下，建立了实用且有效的方法，以实现天然产物的广泛获取。在回顾这些策略时，我们还将重点介绍异源天然产物生物合成的发展，它依赖于理论上具有先进生产潜力的替代宿主系统。在比较天然和异源系统时，我们将评论用于天然产物生物合成的基础生物体，以及此类细胞宿主的特性如何决定规模化工程实践以促进化合物的分布。在文章结尾，我们将研究生产实践中的新成果，这些成果完全消除了细胞生产宿主的限制。也就是说，将引入并综述无细胞生产方法，以用于复杂天然产物的生物合成。在这最后的分析中，将包括我们为测试复杂聚酮类抗生素天然产物红霉素的无细胞生物合成所做的研究工作。
