Successfully interfacing enzymes and biomachineries with polymers affords ondemand modification and/or programmable plastic degradation during manufacture, utilization, and disposal, but requires controlled biocatalysis in solid matrices with macromolecular substrates. [1][2][3][4][5][6][7] Embedded enzyme microparticles have sped up polyester degradation, but compromise host properties and unintentionally accelerate microplastics formation with partial polymer degradation. 6,8,9 Here, by nanoscopically dispersing enzymes with deep active sites, semi-crystalline polyesters can be degraded primarily via chain-end mediated processive depolymerization with programmable latency and material integrity, akin to polyadenylationinduced mRNA decay. 10 It is also feasible to realize the processivity with enzymes having surface-exposed active sites by engineering enzyme/protectant/polymer complexes.Polycaprolactone and poly(lactic acid) containing less than 2 wt.% enzymes are depolymerized in days with up to 98% polymer-to-small molecule conversion in standard soil composts or household tap water, completely eliminating current needs to separate and landfill their products in compost facilities. Furthermore, oxidases embedded in polyolefins retain activities. However, the hydrocarbon polymers do not closely associate with enzymes like their polyester counterparts and the reactive radicals generated cannot chemically modify the macromolecular host. The studies described here provide molecular guidance toward the enzyme/polymer pairing and enzyme protectants' selection to modulate substrate selectivity and optimize biocatalytic pathways. They also highlight the need for in-depth research in solid-state enzymology, especially in multi-step enzymatic cascades, to tackle chemically dormant substrates without creating secondary environmental contamination and/or biosafety concerns.

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Random heteropolymers (RHPs) are an interesting class of materials useful in many theories and applications. While previous studies typically focused on simplified RHP systems, here we explore a more complex scenario inspired by highly heterogeneous molecules like proteins. Our system consists of four monomers mimicking different classes of amino acids. Using Molecular Dynamics simulations and Small-Angle X-Ray Scattering, we explore dynamical and structural features of these RHPs in solution.Our results show the RHPs assemble with heterogeneous interfaces reminiscent of protein surfaces. The polymer backbones appear frozen at room temperature on the nano-to micro-second timescale with molten-globule morphology, albeit their conformational space has multiple metastable conformations for a given sequence, drawing comparison to Intrinsically Disordered Proteins. Local connectivity and chemistry are also shown to have substantial impact on polymer solvation. The work presented here indicates that RHPs share similarities with proteins to be leveraged in bio-mimetic and bio-inspired applications.

G-quadruplex-containing DNAzymes and aptamers are widely applied in many research fields because of their high stability and prominent activities versus the protein counterparts. In this work, G-quadruplex DNAs were equipped with photolabile groups to construct photocaged DNAzymes and aptamers. We incorporated TEEP-OH (thioether-enol phosphate, phenol substituted) into phosphodiester backbone of G-quadruplex DNA by a facile post-synthetic method to achieve efficient photocaging of their activities. Upon light irradiation, the peroxidase-mimicking activity of the caged G-quadruplex DNAzyme was activated, through the transformation of TEEP-OH into a native DNA phosphodiester without any artificial scar. Similarly, the caged G-quadruplex thrombin-binding aptamer also showed light-induced activation of thrombin inhibition activity. This method could serve as a general strategy to prepare photocaged G-quadruplex DNA with other activities for noninvasive control of their functions.

Biological fluids, the most complex blends, have compositions that constantly vary and cannot be molecularly defined1. Despite these uncertainties, proteins fluctuate, fold, function and evolve as programmed2–4. We propose that in addition to the known monomeric sequence requirements, protein sequences encode multi-pair interactions at the segmental level to navigate random encounters5,6; synthetic heteropolymers capable of emulating such interactions can replicate how proteins behave in biological fluids individually and collectively. Here, we extracted the chemical characteristics and sequential arrangement along a protein chain at the segmental level from natural protein libraries and used the information to design heteropolymer ensembles as mixtures of disordered, partially folded and folded proteins. For each heteropolymer ensemble, the level of segmental similarity to that of natural proteins determines its ability to replicate many functions of biological fluids including assisting protein folding during translation, preserving the viability of fetal bovine serum without refrigeration, enhancing the thermal stability of proteins and behaving like synthetic cytosol under biologically relevant conditions. Molecular studies further translated protein sequence information at the segmental level into intermolecular interactions with a defined range, degree of diversity and temporal and spatial availability. This framework provides valuable guiding principles to synthetically realize protein properties, engineer bio/abiotic hybrid materials and, ultimately, realize matter-to-life transformations.