Kong Wentao, Qian Yuanchao, Stewart Philip S, Lu Ting
Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Nat Chem Biol. 2023 Apr;19(4):488-497. doi: 10.1038/s41589-022-01194-1. Epub 2022 Dec 15.
Synthetic biology has shown remarkable potential to program living microorganisms for applications. However, a notable discrepancy exists between the current engineering practice-which focuses predominantly on planktonic cells-and the ubiquitous observation of microbes in nature that constantly alternate their lifestyles on environmental variations. Here we present the de novo construction of a synthetic genetic program that regulates bacterial life cycle and enables phase-specific gene expression. The program is orthogonal, harnessing an engineered protein from 45 candidates as the biofilm matrix building block. It is also highly controllable, allowing directed biofilm assembly and decomposition as well as responsive autonomous planktonic-biofilm phase transition. Coupling to synthesis modules, it is further programmable for various functional realizations that conjugate phase-specific biomolecular production with lifestyle alteration. This work establishes a versatile platform for microbial engineering across physiological regimes, thereby shedding light on a promising path for gene circuit applications in complex contexts.
合成生物学在对活微生物进行编程以实现各种应用方面已展现出显著潜力。然而，当前主要聚焦于浮游细胞的工程实践与自然界中微生物随环境变化不断交替生活方式这一普遍观察结果之间存在明显差异。在此，我们展示了一种从头构建的合成遗传程序，该程序可调节细菌生命周期并实现阶段特异性基因表达。该程序具有正交性，利用从45种候选蛋白中筛选出的一种工程蛋白作为生物膜基质构建模块。它还具有高度可控性，能够实现定向生物膜组装与分解以及响应性自主浮游 - 生物膜相变。与合成模块相结合，它可进一步编程以实现各种功能，将阶段特异性生物分子生产与生活方式改变相结合。这项工作建立了一个跨生理状态的通用微生物工程平台，从而为复杂环境中基因回路的应用开辟了一条充满希望的道路。
