A Peptide-Based Oscillator

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.