Early evolution benefited from a complex network of reactions involving multiple C−C bond forming and breaking events that were critical for primitive metabolism. Nature gradually chose highly evolved and complex enzymes such as lyases to efficiently facilitate C−C bond formation and cleavage with remarkable substrate selectivity. Reported here is a lipidated short peptide which accesses a homogenous nanotubular morphology to efficiently catalyze C−C bond cleavage and formation. This system shows morphology‐dependent catalytic rates, suggesting the formation of a binding pocket and registered enhancements in the presence of the hydrogen‐bond donor tyrosine, which is exploited by extant aldolases. These assemblies showed excellent substrate selectivity and templated the formation of a specific adduct from a pool of possible adducts. The ability to catalyze metabolically relevant cascade transformations suggests the importance of such systems in early evolution.

We report the generation of simple condensates of short peptides with ATP, which are spatiotemporally formed under dissipative conditions and temporally modulate a secondary redox reaction catalyzed by the entrapped protein.

The review focuses on the recent developments on diverse sets of complex enzymatic transformations by utilizing minimal peptide based self-assembled systems. It further attempts to provide a broad perspective for potentially programming functionality via rational selection of amino acid sequences, leading towards minimal catalytic systems that emulate some advanced traits of contemporary enzymes.

Peptide-based biomimetic catalysts are promising materials for efficient catalytic activity in various biochemical transformations. However, their lack of operational stability and fragile nature in non-aqueous media limit their practical applications. In this study, we have developed a cladding technique to stabilize biomimetic catalysts within porous covalent organic framework (COF) scaffolds. This methodology allows for the homogeneous distribution of peptide nanotubes inside the COF (TpAzo and TpDPP) backbone, creating strong noncovalent interactions that prevent leaching. We synthesized two different peptide-amphiphiles, C10FFVK and C10FFVR, with lysine (K) and arginine (R) at the C-termini, respectively, which formed nanotubular morphologies. The C10FFVK peptide-amphiphile nanotubes exhibit enzyme-like behavior and efficiently catalyze C–C bond cleavage in a buffer medium (pH 7.5). We produced nanotubular structures of TpAzo–C10FFVK and TpDPP–C10FFVK through COF cladding by using interfacial crystallization (IC). The peptide nanotubes encased in the COF catalyze C–C bond cleavage in a buffer medium as well as in different organic solvents (such as acetonitrile, acetone, and dichloromethane). The TpAzo–C10FFVK catalyst, being heterogeneous, is easily recoverable, enabling the reaction to be performed for multiple cycles. Additionally, the synthesis of TpAzo–C10FFVK thin films facilitates catalysis in flow. As control, we synthesized another peptide-amphiphile, C10FFVR, which also forms tubular assemblies. By depositing TpAzo COF crystallites on C10FFVR nanotubes through IC, we produced TpAzo–C10FFVR nanotubular structures that expectedly did not show catalysis, suggesting the critical role of the lysines in the TpAzo–C10FFVK.

Herein, we report the substrate induced generation of a transient catalytic microenvironment from a single amino acid functionalized fatty acid in presence of a cofactor hemin. The catalytic state accessed under non-equilibrium conditions showed acceleration of peroxidase activity resulting in degradation of the substrate and subsequently led to disassembly. Equilibrated systems could not access the three-dimensional microphases and showed substantially lower catalytic activity. Further, the assembled state showed latent catalytic function (promiscuity) to hydrolyze a precursor to yield the same substrate. Consequently, the assembly demonstrated protometabolism by exploiting the peroxidase-hydrolase cascade to augment the lifetime and the mechanical properties of the catalytic state.

Herein, we report the substrate induced generation of a transient catalytic microenvironment from a single amino acid functionalized fatty acid in presence of a cofactor hemin. The catalytic state accessed under non-equilibrium conditions showed acceleration of peroxidase activity resulting in degradation of the substrate and subsequently led to disassembly. Equilibrated systems could not access the three-dimensional microphases and showed substantially lower catalytic activity. Further, the assembled state showed latent catalytic function (promiscuity) to hydrolyze a precursor to yield the same substrate. Consequently, the assembly demonstrated protometabolism by exploiting the peroxidase-hydrolase cascade to augment the lifetime and the mechanical properties of the catalytic state.

Extant proteins exploit thermodynamically activated negatively charged coenzymes and hydrotropes to temporally access mechanistically important conformations that regulate vital biological functions, from metabolic reactions to expression modulation. Herein, we show that a short amyloid peptide can bind to a small molecular coenzyme by exploiting reversible covalent linkage to polymerize and access catalytically proficient nonequilibrium amyloid microphases. Subsequent hydrolysis of the activated coenzyme leads to depolymerization, realizing a variance of the surface charge of the assembly as a function of time. Such temporal change of surface charge dynamically modulates catalytic activities of the transient assemblies as observed in highly evolved modern-day biocatalysts.

Thixotropic and self‐healable supramolecular gel with nanohelical morphological features of discotic C3 symmetric benzene‐1,3,5‐tricarboxylic acid coupled with (L)‐ and (D)‐phenylalanine were achieved by hydroxyl anion catalysed methyl ester hydrolysis in presence of lithium ions. The hydrolysis of methyl ester and subsequent formation of gel are highly dependent on metal ions. The arrangement of the molecular building blocks and increasing the structural complexity during the origin of the supramolecular structures from the monomeric units by a chemical reaction act as the executive parameters to determine the handedness of macroscopic chirality.