This Review is aimed at synthetic organic chemists who may be familiar with organometallic catalysis but have no experience with biocatalysis, and seeks to provide an answer to the perennial question: if it is so attractive, why wasn't it extensively used in the past? The development of biocatalysis in industrial organic synthesis is traced from the middle of the last century. Advances in molecular biology in the last two decades, in particular genome sequencing, gene synthesis and directed evolution of proteins, have enabled remarkable improvements in scope and substantially reduced biocatalyst development times and cost contributions. Additionally, improvements in biocatalyst recovery and reuse have been facilitated by developments in enzyme immobilization technologies. Biocatalysis has become eminently competitive with chemocatalysis and the biocatalytic production of important pharmaceutical intermediates, such as enantiopure alcohols and amines, has become mainstream organic synthesis. The synthetic space of biocatalysis has significantly expanded and is currently being extended even further to include new-to-nature biocatalytic reactions.

Broadening the Scope of Biocatalysis in Sustainable Organic Synthesis

The design of bioactive supramolecular chirality is always hampered by the lack of feasible schemes to assigned specific biological activities Herein, we developed a "mirror-image peptide grafting" method to graft the epitopes of bioactive d-peptide onto the miniprotein template to construct a self-assembled supraparticle Grafting DPMIβ, a 12-mer d-enantiomeric peptide functioned as the p53 agonist, onto Apamin, we successfully constructed a self-assembled d-enantiomeric miniprotein supermolecule nanoparticle, termed DMSN This chiral supraparticle possesses a favorable pharmaceutical profile including the passive tumor targeting, cell membrane penetration, intracellular reductive responsiveness, and endosome escaping DMSN showed in vitro and in vivo p53-dependent antiproliferative activity and augmented antitumor immunity elicited by anti-PD1 therapy This enabling strategy will allow us to fabricate a class of peptide/protein-derived supramolecular chirality with predictable biological activities and will likely have a broad impact on the chiral nanotechnology at the service of prevention and treatment of human diseases

Chiral Protein Supraparticles for Tumor Suppression and Synergistic Immunotherapy: An Enabling Strategy for Bioactive Supramolecular Chirality Construction

Exploration of molecular functions and material properties based on the control of chirality would be a scientifically elegant approach. Here, the fabrication and function of chiral-featured materials from both chiral and achiral components using a supramolecular nanoarchitectonics concept are discussed. The contents are classified in to three topics: i) chiral nanoarchitectonics of rather general molecular assemblies; ii) chiral nanoarchitectonics of metal-organic frameworks (MOFs); iii) chiral nanoarchitectonics in liquid crystals. MOF structures are based on nanoscopically well-defined coordinations, while mesoscopic orientations of liquid-crystalline phases are often flexibly altered. Discussion on the effects and features in these representative materials systems with totally different natures reveals the universal importance of supramolecular chiral nanoarchitectonics. Amplification of chiral molecular information from molecules to materials-level structures and the creation of chirality from achiral components upon temporal statistic fluctuations are universal, regardless of the nature of the assemblies. These features are thus surely advantageous characteristics for a wide range of applications.

Supramolecular Chiral Nanoarchitectonics.

Thermostability is considered to be an important parameter to measure the feasibility of enzymes for industrial applications. Generally, higher thermostability makes an enzyme more competit...

Recent advances in the improvement of enzyme thermostability by structure modification.

Chirality is ubiquitous in nature and hard-wired into every biological system. Despite the prevalence of chirality in biological systems, controlling biomaterial chirality to influence interactions with cells has only recently been explored. Chiral-engineered supraparticles (SPs) that interact differentially with cells and proteins depending on their handedness are presented. SPs coordinated with d-chirality demonstrate greater than threefold enhanced cell membrane penetration in breast, cervical, and multiple myeloma cancer cells. Quartz crystal microbalance with dissipation and isothermal titration calorimetry measurements reveal the mechanism of these chiral-specific interactions. Thermodynamically, d-SPs show more stable adhesion to lipid layers composed of phospholipids and cholesterol compared to l-SPs. In vivo, d-SPs exhibit superior stability and longer biological half-lives likely due to opposite chirality and thus protection from endogenous proteins including proteases. This work shows that incorporating d-chirality into nanosystems enhances uptake by cancer cells and prolonged in vivo stability in circulation, providing support for the importance of chirality in biomaterials. Thus, chiral nanosystems may have the potential to provide a new level of control for drug delivery systems, tumor detection markers, biosensors, and other biomaterial-based devices.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.201903878

Chiral Supraparticles for Controllable Nanomedicine.

Chiral amino acids are extensively applied in the pharmaceutical, food, cosmetic, agricultural, and feedstuff industries. The development of synthetic methodologies for optically pure amino acids has been driven by their significant applications. Among the various synthesis methods for the production of chiral amino acids, enzymatic asymmetric synthesis is a unique preparation strategy that shows great potential. This review provides an overview of the reported methods for enzymatic asymmetric synthesis of chiral amino acids, including asymmetric reductive amination of keto acids, asymmetric transfer of an amino group to keto acids, enantioselective addition of ammonia to α,β-unsaturated acids, and aldol condensation of an amino acid to aldehydes.

Enzymatic asymmetric synthesis of chiral amino acids.

Enzyme cascade for biocatalytic deracemization of D,L-phosphinothricin

Efficient synthesis of L-phosphinothricin using a novel aminoacylase mined from Stenotrophomonas maltophilia.

2-Oxo-4-(hydroxymethylphosphinyl) butyric acid (PPO) is an important precursor compound for the broad-spectrum herbicide l-glufosinate (L-PPT). In this study, the gene of d-amino acid oxidase (DAAO...

Development of a biocatalytic cascade for synthesis of 2-oxo-4-(hydroxymethylphosphinyl) butyric acid in one pot

The invention discloses a glufosinate dehydrogenase mutant and application thereof. The glufosinate dehydrogenase mutant is obtained by single mutation or multiple mutation of the 90th, 91st and 376thamino acid shown in SEQ ID No.2; the 90th lysine is mutated to serine; the 91th glycine is mutated to serine or valine; the 376th serine is mutated into arginine. The mutant utilizes a site-directedsaturation mutation technique for mutation of the glufosinate dehydrogenase gene shown in SEQ ID No.1, and finds that the 90th, 91st, and 376th positions are key sites affecting the enzyme activity, the obtained specific enzyme activity is much higher than the mutant of the parental glufosinate dehydrogenase, the specific enzyme activity of the mutant lvPDH-K90S-G91P-S376R is 8.4 times higher thanthat of the parental glufosinate dehydrogenase, and the mutant has industrial application prospects.

Cao Chenghao

Papers

Enzymatic asymmetric synthesis of chiral amino acids.

Enzyme cascade for biocatalytic deracemization of D,L-phosphinothricin

Efficient synthesis of L-phosphinothricin using a novel aminoacylase mined from Stenotrophomonas maltophilia.

Development of a biocatalytic cascade for synthesis of 2-oxo-4-(hydroxymethylphosphinyl) butyric acid in one pot

Glufosinate dehydrogenase mutant and application thereof