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Non-proteinaceous hydrolase comprised of a phenylalanine metallo-supramolecular amyloid-like structure.

ABSTRACT: Enzymatic activity is crucial for various technological applications, yet the complex structures and limited stability of enzymes often hinder their use. Hence, de novo design of robust biocatalysts that are much simpler than their natural counterparts and possess enhanced catalytic activity has long been a goal in biotechnology. Here, we present evidence for the ability of a single amino acid to self-assemble into a potent and stable catalytic structural entity. Spontaneously, phenylalanine (F) molecules coordinate with zinc ions to form a robust, layered, supramolecular amyloid-like ordered architecture (F-Zn(ii)) and exhibit remarkable carbonic anhydrase-like catalytic activity. Notably, amongst the reported artificial biomolecular hydrolases, F-Zn(ii) displays the lowest molecular mass and highest catalytic efficiency, in addition to reusability, thermal stability, substrate specificity, stereoselectivity and rapid catalytic CO2 hydration ability. Thus, this report provides a rational path towards future de novo design of minimalistic biocatalysts for biotechnological and industrial applications.

SUBMITTER: Makam P

PROVIDER: S-EPMC6861134 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Non-proteinaceous hydrolase comprised of a phenylalanine metallo-supramolecular amyloid-like structure.

Makam Pandeeswar P Yamijala Sharma S R K C SSRKC Tao Kai K Shimon Linda J W LJW Eisenberg David S DS Sawaya Michael R MR Wong Bryan M BM Gazit Ehud E

Nature catalysis 20190923 11

Enzymatic activity is crucial for various technological applications, yet the complex structures and limited stability of enzymes often hinder their use. Hence, de novo design of robust biocatalysts that are much simpler than their natural counterparts and possess enhanced catalytic activity has long been a goal in biotechnology. Here, we present evidence for the ability of a single amino acid to self-assemble into a potent and stable catalytic structural entity. Spontaneously, phenylalanine (F) ...[more]

PMID: 31742246

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Project description:Supramolecular hydrogels have emerged as a class of promising biomaterials for applications such as drug delivery and tissue engineering. Self-assembling peptides have been well studied for such applications, but low molecular weight (LMW) amino acid-derived gelators have attracted interest as low-cost alternatives with similar emergent properties. Fluorenylmethyloxycarbonyl-phenylalanine (Fmoc-Phe) is one such privileged motif often chosen due to its inherent self-assembly potential. Previously, we developed cationic Fmoc-Phe-DAP gelators that assemble into hydrogel networks in aqueous NaCl solutions of sufficient ionic strength. The chloride anions in these solutions screen the cationic charge of the gelators to enable self-assembly to occur. Herein, we report the effects of varying the anions of sodium salts on the gelation potential, nanoscale morphology, and hydrogel viscoelastic properties of Fmoc-Phe-DAP and two of its fluorinated derivatives, Fmoc-3F-Phe-DAP and Fmoc-F5-Phe-DAP. It was observed that both the anion identity and gelator structure had a significant impact on the self-assembly and gelation properties of these derivatives. Changing the anion identity resulted in significant polymorphism of the nanoscale morphology of the assembled states that was dependent on the chemical structure of the gelator. The emergent viscoelastic character of the hydrogel networks was also found to be reliant on the anion identity and gelator structure. These results demonstrate the complex interplay between the gelator and environment that have a profound and often unpredictable impact on both self-assembly properties and emergent viscoelasticity in supramolecular hydrogels formed by LMW compounds. This work also illustrates the current lack of understanding that limits the rational design of potential biomaterials that will be in contact with complex biological fluids and provides motivation for additional research to correlate the chemical structure of LMW gelators with the structure and emergent properties of the resulting supramolecular assemblies as a function of environment.

Project description:Supramolecular hydrogels formed by self-assembly of low molecular weight (LMW) compounds have been identified as promising materials for applications in tissue engineering and regenerative medicine. In many cases, the relationship between the chemical structure of the gelator and the emergent hydrogel properties is poorly understood. As a result, empirical screening strategies instead of rational design approaches are often relied upon to tune the emergent properties of the gels. Herein, we describe a novel strategy to identify improved phenylalanine (Phe) derived gelators using a focused empirical approach. Fluorenylmethoxycarbonyl (Fmoc) protected Phe derivatives are a privileged class of gelators that spontaneously self-assemble into fibrils that entangle to form a hydrogel network upon dissolution into water. However, the Fmoc group has been shown to have toxicity drawbacks for potential biological applications, requiring the identification of new N-terminal modifications that promote efficient self-assembly but lack the shortcomings of the Fmoc group. We previously discovered that fibrils in Fmoc-p-nitrophenylalanine (Fmoc-4-NO2-Phe) hydrogels transition to crystalline microtubes after several hours by a mechanism that involves the hierarchical assembly and fusion of the hydrogel fibrils. We hypothesized that this hierarchical crystallization behavior could form the basis of a screening approach to identify alternative N-terminal functional groups to replace Fmoc in Phe-derived LMW gelators. Specifically, screening N-terminal modifying groups for 4-NO2-Phe that stabilize the hydrogel state by preventing subsequent hierarchical crystallization would facilitate empirical identification of functional Fmoc replacements. To test this approach, we screened a small series of 4-NO2-Phe derivatives with various N-terminal modifying groups to determine if any provided stable LMW supramolecular hydrogels. All but one of the 4-NO2-Phe derivatives assembled into crystalline forms. Only the 1-naphthaleneacetic acid (1-Nap) 4-NO2-Phe derivative self-assembled into a stable hydrogel network. Additional Phe derivatives were modified by N-terminal 1-Nap groups to confirm the general potential of 1-Nap as a suitable replacement for Fmoc, and all derivatives formed stable hydrogels under similar conditions to their Fmoc-Phe counterparts. These results illustrate the potential of this approach to identify next-generation Phe-derived LMW gelators with improved emergent properties.

Dataset Information

Non-proteinaceous hydrolase comprised of a phenylalanine metallo-supramolecular amyloid-like structure.

Publications

Non-proteinaceous hydrolase comprised of a phenylalanine metallo-supramolecular amyloid-like structure.

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