Temperature compensation through kinetic regulation in biochemical oscillators.

Nearly all circadian clocks maintain a period that is insensitive to temperature changes, a phenomenon known as temperature compensation (TC). Yet, it is unclear whether there is any common feature among different systems that exhibit TC. From a general timescale invariance, we show that TC relies on the existence of certain period-lengthening reactions wherein the period of the system increases strongly with the rates in these reactions. By studying several generic oscillator models, we show that this counterintuitive dependence is nonetheless a common feature of oscillators in the nonlinear (far-from-onset) regime where the oscillation can be separated into fast and slow phases. The increase of the period with the period-lengthening reaction rates occurs when the amplitude of the slow phase in the oscillation increases with these rates while the progression speed in the slow phase is controlled by other rates of the system. The positive dependence of the period on the period-lengthening rates balances its inverse dependence on other kinetic rates in the system, which gives rise to robust TC in a wide range of parameters. We demonstrate the existence of such period-lengthening reactions and their relevance for TC in all four model systems we considered. Theoretical results for a model of the Kai system are supported by experimental data. A study of the energy dissipation also shows that better TC performance requires higher energy consumption. Our study unveils a general mechanism by which a biochemical oscillator achieves TC by operating in parameter regimes far from the onset where period-lengthening reactions exist.

Covalent Organic Frameworks for Extracting Water from Air.

Water scarcity is becoming an increasingly pressing issue due to global population growth and industrialization. One effective approach to addressing this issue is sorption-based atmospheric water harvesting (SAWH). Covalent organic frameworks (COFs) are a type of porous crystalline material that have emerged as promising sorbents for water harvesting due to their high surface area, tunable pore size, and customizable pore chemistry. In this mini-review, we provide an overview of the different types of COFs, their structural characteristics, and the diverse linkage chemistries used to construct them. Then, we summarize recent advances in using COF-based sorbents for atmospheric water harvesting, including strategies for controlling sorption properties and optimizing performance in terms of thermodynamics and dynamics. Finally, we discuss prospects and challenges associated with improving the efficiency of COF-based SAWH systems.

Quantitative and predictive model of kinetic regulation by E. coli TPP riboswitches.

Riboswitches are non-coding elements upstream or downstream of mRNAs that, upon binding of a specific ligand, regulate transcription and/or translation initiation in bacteria, or alternative splicing in plants and fungi. We have studied thiamine pyrophosphate (TPP) riboswitches regulating translation of thiM operon and transcription and translation of thiC operon in E. coli, and that of THIC in the plant A. thaliana. For all, we ascertained an induced-fit mechanism involving initial binding of the TPP followed by a conformational change leading to a higher-affinity complex. The experimental values obtained for all kinetic and thermodynamic parameters of TPP binding imply that the regulation by A. thaliana riboswitch is governed by mass-action law, whereas it is of kinetic nature for the two bacterial riboswitches. Kinetic regulation requires that the RNA polymerase pauses after synthesis of each riboswitch aptamer to leave time for TPP binding, but only when its concentration is sufficient. A quantitative model of regulation highlighted how the pausing time has to be linked to the kinetic rates of initial TPP binding to obtain an ON/OFF switch in the correct concentration range of TPP. We verified the existence of these pauses and the model prediction on their duration. Our analysis also led to quantitative estimates of the respective efficiency of kinetic and thermodynamic regulations, which shows that kinetically regulated riboswitches react more sharply to concentration variation of their ligand than thermodynamically regulated riboswitches. This rationalizes the interest of kinetic regulation and confirms empirical observations that were obtained by numerical simulations.

Molecular modification of a halohydrin dehalogenase for kinetic regulation to synthesize optically pure (S)-epichlorohydrin.

Asymmetric synthesis of chiral epichlorohydrin (ECH) from 1,3-dichloro-2-propanol (1,3-DCP) using halohydrin dehalogenases (HHDHs) is of great value due to the 100% theoretical yield and high enantioselectivity. The vital problem in the asymmetric synthesis is to prepare optically pure ECH. In this study, key amino acid residues located at halide ion channels of HheC (P175S/W249P) (HheCPS) were modified to regulate the kinetic parameters. HheCPS I81W, F86N and V94R were constructed with the corresponding halide ion channels destroyed. The catalytically efficiencies (kcat/Km) of the three mutants exhibited 0.38-, 0.23- and 0.23-fold decrease toward (S)-ECH and the reverse reaction was significantly inhibited. As the results, (S)-ECH was synthesized with >99% enantiomeric excess (e.e.) and 63.42%, 67.08% and 57.01% yields, respectively, under 20 mM 1,3-DCP as substrate. To our knowledge, this is the first investigation of the molecule kinetic modification of HHDHs and also the first report for the biosynthesis of optically pure (S)-ECH from 1,3-DCP using HHDHs.

Programming Chemical Reaction Networks Using Intramolecular Conformational Motions of DNA.

The programmable regulation of chemical reaction networks (CRNs) represents a major challenge toward the development of complex molecular devices performing sophisticated motions and functions. Nevertheless, regulation of artificial CRNs is generally energy- and time-intensive as compared to natural regulation. Inspired by allosteric regulation in biological CRNs, we herein develop an intramolecular conformational motion strategy (InCMS) for programmable regulation of DNA CRNs. We design a DNA switch as the regulatory element to program the distance between the toehold and branch migration domain. The presence of multiple conformational transitions leads to wide-range kinetic regulation spanning over 4 orders of magnitude. Furthermore, the process of energy-cost-free strand exchange accompanied by conformational change discriminates single base mismatches. Our strategy thus provides a simple yet effective approach for dynamic programming of complex CRNs.