Biocatalytic reaction networks integrate complex cascade transformations via spatial localization of multiple enzymes confined within the cellular milieu. Inspired by natures ingenuity, we demonstrate that short peptide-based cross-b amyloid nanotubular hybrids can promote different kinds of cascade reactions, from simple two-step, to multistep, to complex convergent cascades. The compartmentalizing ability of paracrystalline cross-b phases was utilized to colocalize sarcosine oxidase (SOX) and hemin as an artificial peroxidase. Further, the catalytic potential of the amyloid nanotubes with ordered arrays of imidazoles were used as hydrolase mimic. The SOX-hemin amyloid nanohybrids featuring a single extant enzyme could integrate different logic networks to access complex digital designs with the help of three concatenated AND gates and biologically relevant stimuli as inputs.

The development of synthetic nonequilibrium systems has gathered increasing attention due to their potential to illustrate the dynamic, complex, and emergent traits of biological systems. Simple building blocks capable of interacting via dynamic covalent chemistry and physical assembly in a reaction network under nonequilibrium conditions can contribute to our understanding of complex systems of life and its origin. Herein, we have demonstrated the nonequilibrium generation of catalytic supramolecular assemblies from simple heterocycle melamine driven by a thermodynamically activated ester. Utilizing a reversible covalent linkage, an imidazole moiety was recruited by the assemblies to access a catalytic transient state that dissipated energy via accelerated hydrolysis of the activated ester. The nonequilibrium assemblies were further capable of temporally binding to a hydrophobic guest to modulate its photophysical properties. Notably, the presence of an exogenous aromatic base augmented the lifetime of the catalytic microphases, reflecting their higher kinetic stability.

Biocatalytic reaction networks integrate complex cascade transformations via spatial localization of multiple enzymes confined within the cellular milieu. Inspired by natures ingenuity, we demonstrate that short peptide-based cross-b amyloid nanotubular hybrids can promote different kinds of cascade reactions, from simple two-step, to multistep, to complex convergent cascades. The compartmentalizing ability of paracrystalline cross-b phases was utilized to colocalize sarcosine oxidase (SOX) and hemin as an artificial peroxidase. Further, the catalytic potential of the amyloid nanotubes with ordered arrays of imidazoles were used as hydrolase mimic. The SOX-hemin amyloid nanohybrids featuring a single extant enzyme could integrate different logic networks to access complex digital designs with the help of three concatenated AND gates and biologically relevant stimuli as inputs.

Herein, we report that short peptides are capable of exploiting their anti-parallel registry to access cross-β stacks to expose more than one catalytic residue, exhibiting the traits of advanced binding...

<p>Bioenergetics played critical roles for the chemical emergence of life where available energy resources drove the generation of primitive polymers and fueled early metabolism. Further, apart from information storage, the catalytic roles of primitive nucleic acid fragments have also been argued to be important for biopolymer evolution. Herein, we have demonstrated the non-equilibrium generation of catalytic supramolecular polymers of a possible proto-RNA building block (melamine) driven by a thermodynamically activated ester of low molecular weight. We utilized reversible covalent linkage to install a catalytic imidazole moiety in the polymer backbone. This resulted in energy dissipation via hydrolysis of the substrate predominantly from the assembled state and subsequent disassembly, thus installing kinetic asymmetry in the energy consumption cycle. Non-catalytic analogues led to kinetically stable polymers while inactivated substrates were unable to drive the polymerization. The non-equilibrium polymers of the pre-RNA bases were capable to spatiotemporally bind to a model cofactor. Notably, presence of an exogenous aromatic base augmented the stability of the polymers, reminiscent to what the molecular midwives did during early evolution. </p>