Directed Evolution and Unusual Protonation Mechanism of Pyridoxal Radical C–C Coupling Enzymes for the Enantiodivergent Photobiocatalytic Synthesis of Noncanonical Amino Acids

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Visible light-driven pyridoxal radical biocatalysis has emerged as a new strategy for the stereoselective synthesis of valuable noncanonical amino acids in protecting-group-free fashion. In our previously developed dehydroxylative C–C coupling using engineered PLP-dependent tryptophan synthases, an enzyme-controlled unusual α-stereochemistry reversal and pH-controlled enantiopreference were observed. Herein, through high-throughput photobiocatalysis, we evolved set stereochemically complementary PLP enzymes, allowing both l- d-amino with enhanced enantiocontrol across broad pH window. These newly acid synthases permitted use range organoboron substrates, including boronates, trifluoroborates, boronic acids, excellent efficiency. Mechanistic studies unveiled unexpected racemase activity earlier enzyme variants. This promiscuous was abolished shedding light on origin enantiocontrol. Further mechanistic investigations suggest switch proton donor to account stereoinvertive formation highlighting stereoinversion mechanism that is rare conventional two-electron enzymology.

Language: Английский

Threonine Aldolase-Catalyzed Enantioselective α-Alkylation of Amino Acids through Unconventional Photoinduced Radical Initiation

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(32), P. 22476 - 22484

Published: July 4, 2024

Visible light-driven pyridoxal radical biocatalysis has emerged as a promising strategy for the stereoselective synthesis of valuable noncanonical amino acids (ncAAs). Previously, use well-tailored photoredox catalysts represented key to enable efficient phosphate (PLP) enzyme-catalyzed reactions. Here, we report PLP-dependent threonine aldolase-catalyzed asymmetric α-C–H alkylation abundant using Katritzky pyridinium salts alkylating agents. The engineered aldolases allowed this redox-neutral proceed efficiently, giving rise challenging α-trisubstituted and -tetrasubstituted ncAA products in protecting-group-free fashion with excellent enantiocontrol. Mechanistically, enantioselective α-alkylation capitalizes on unique reactivity persistent enzymatic quinonoid intermediate derived from PLP cofactor acid substrate allow novel C–C coupling. Surprisingly, photobiocatalytic process does not require well-established operates through an unconventional photoinduced generation involving PLP-derived aldimine. ability develop reactions without relying classic photocatalysts or photoenzymes opens up new avenues advancing intermolecular that are known either organic chemistry enzymology.

Language: Английский

Modular Access from Acrylate to a Sustainable Polyester Platform with Large-Span Tunability and Chemical Circularity under Mild Conditions

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Making polyesters with conventional vinyl monomers is one of the most economical ways to develop sustainable polymeric materials. For polar vinyls, while their transformation into lactones has been studied extensively, there exists no further access synthesizing polyesters, presumably due nonstrained and nonpolymerizable nature obtained lactones. Herein, we report first facile synthesis that originated from critical classes vinyls-acrylates. Specifically, a series modular six-membered were rationally designed synthesized methyl acrylate together malonic esters containing diverse functional groups formaldehyde. The underwent ring-opening polymerization (ROP) yield acrylate-derived which constitute unique polymer platform large scope potential functionalities performances as well easy chemical circularity under mild conditions. Notably, are rare example featuring tunable on side ester whose impact certain material properties (e.g., glass transition temperature) similar polyacrylates, implying replacement between polyacrylates. In addition, by presenting special geminal disubstitutions originally monomers' γ-position for time, also exhibited unprecedentedly enhanced thermal recycling properties: Variation offers large-span modulation completely amorphous high-level crystalline materials, melting temperature high crystallinity was drastically increased 84 °C compared reported monosubstituted counterpart. At same other required harsh conditions (>150 vacuum), gem-disubstituted in this work can undergo complete much milder (80 ambient pressure). This study informs design future high-performance derived vinyls.

Language: Английский