Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, California 94608, United States.
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.
ACS Synth Biol. 2023 Nov 17;12(11):3148-3155. doi: 10.1021/acssynbio.3c00282. Epub 2023 Oct 23.
Polyketide retrobiosynthesis, where the biosynthetic pathway of a given polyketide can be reversibly engineered due to the colinearity of the polyketide synthase (PKS) structure and function, has the potential to produce millions of organic molecules. Mixing and matching modules from natural PKSs is one of the routes to produce many of these molecules. Evolutionary analysis of PKSs suggests that traditionally used module boundaries may not lead to the most productive hybrid PKSs and that new boundaries around and within the ketosynthase domain may be more active when constructing hybrid PKSs. As this is still a nascent area of research, the generality of these design principles based on existing engineering efforts remains inconclusive. Recent advances in structural modeling and synthetic biology present an opportunity to accelerate PKS engineering by re-evaluating insights gained from previous engineering efforts with cutting edge tools.
聚酮类化合物的反式生物合成，由于聚酮合酶 (PKS) 的结构和功能的线性关系，给定的聚酮类化合物的生物合成途径可以可逆地进行工程改造，具有产生数百万种有机分子的潜力。混合和匹配天然 PKS 的模块是产生其中许多分子的途径之一。对 PKS 的进化分析表明，传统上使用的模块边界可能不会导致最具生产力的杂交 PKS，并且在构建杂交 PKS 时，围绕和在酮合酶结构域内的新边界可能更活跃。由于这仍然是一个新兴的研究领域，基于现有工程努力的这些设计原则的普遍性仍然没有定论。结构建模和合成生物学的最新进展为通过使用最先进的工具重新评估从以前的工程努力中获得的见解来加速 PKS 工程提供了机会。
