Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Centre for Nano and Material Sciences, Jain Global Campus, Bangalore, Karnataka 560070, India.
J Am Chem Soc. 2023 Dec 6;145(48):26279-26286. doi: 10.1021/jacs.3c09377. Epub 2023 Nov 20.
Living organisms are replete with rhythmic and oscillatory behavior at all levels, to the extent that oscillations have been termed as a defining attribute of life. Recent studies of synthetic oscillators that mimic such functions have shown decayed cycles in batch-mode reactions or sustained oscillatory kinetics under flow conditions. Considering the hypothesized functionality of peptides in early chemical evolution and their central role in current bio-nanotechnology, we now reveal a peptide-based oscillator. Oscillatory behavior was achieved by coupling coiled-coil-based replication processes as positive feedback to controlled initiation and inhibition pathways in a continuously stirred tank reactor (CSTR). Our results stress that assembly into the supramolecular structure and specific interactions with the replication substrates are crucial for oscillations. The replication-inhibition processes were first studied in batch mode, which produced a single damped cycle. Thereafter, combined experimental and theoretical characterization of the replication process in a CSTR under different flow and environmental (pH, redox) conditions demonstrated reasonably sustained oscillations. We propose that studies in this direction might pave the way to the design of robust oscillation networks that mimic the autonomous behavior of proteins in cells (e.g., in the cyanobacterial circadian clock) and hence hint at feasible pathways that accelerated the transition from simple peptides to extant enzymes.
生物体在各个层次都充满了有节奏和振荡的行为，以至于振荡已被称为生命的定义属性。最近对模仿此类功能的合成振荡器的研究表明，批处理反应中的循环衰退或在流动条件下持续的振荡动力学。考虑到在早期化学进化中肽的假设功能及其在当前生物纳米技术中的核心作用，我们现在揭示了一种基于肽的振荡器。通过将基于卷曲螺旋的复制过程耦合为正反馈，来实现振荡行为，以控制连续搅拌釜式反应器 (CSTR) 中的起始和抑制途径。我们的结果强调了组装成超分子结构以及与复制底物的特定相互作用对于振荡的重要性。复制抑制过程首先在批处理模式下进行研究，产生了单个阻尼周期。此后，在不同的流动和环境 (pH、氧化还原) 条件下在 CSTR 中对复制过程进行的组合实验和理论表征证明了相当稳定的振荡。我们提出，朝着这个方向的研究可能为设计模仿细胞中蛋白质自主行为的稳健振荡网络铺平道路（例如，在蓝藻生物钟中），从而暗示加速从简单肽到现存酶的转变的可行途径。
