Article
Chemistry, Multidisciplinary
Felipe Ospina, Kai H. Schuelke, Jordi Soler, Alina Klein, Benjamin Prosenc, Marc Garcia-Borras, Stephan C. Hammer
Summary: This study reports a new method for regioselective N-methylation of unsaturated heterocycles. By using two methyltransferases and simple reagents, important molecules with biological activities can be synthesized efficiently.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Xiaojin Wen, Florian Leisinger, Viviane Leopold, Florian P. Seebeck
Summary: Late-stage methylation is a crucial technology in pharmaceutical compound development. Methyltransferase biocatalysis offers a powerful option for inserting methyl groups into complex molecules with high selectivity. However, large-scale application of methyltransferases is hindered by the expensive S-adenosylmethionine (SAM) co-substrate and the handling of volatile electrophiles like methyl iodide (MeI). To overcome these challenges, researchers have developed an enzyme-catalyzed process using methyl toluene sulfonate for SAM regeneration.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Jiaming Peng, Cangsong Liao, Carsten Bauer, Florian P. Seebeck
Summary: Strategically replacing protons with fluorine atoms or functional groups has proven to be an effective way to optimize the activity of therapeutic compounds, leading to intense development in the field of organofluorides. However, literature on fluorine biocatalysis is still limited, with the introduction of SAM-dependent methyltransferases as a new tool for producing fluorinated compounds being a key innovation in the field. This approach demonstrates the ability of halide methyltransferases to form unstable fluorinated SAM, accepted as a substrate by specific methyltransferases for enzyme-catalyzed fluoromethylation of small molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Lucy C. Ward, Hannah McCue, Daniel J. Rigden, Neil M. Kershaw, Chloe Ashbrook, Harry Hatton, Ellie Goulding, James R. Johnson, Andrew J. Carnell
Summary: Carboxyl methyltransferase enzymes from Aspergillus fumigatus showed high regioselectivity and good conversions in methylating a broad range of aromatic mono- and dicarboxylic acids. The second methylation of dicarboxylic acids exhibited strong pH dependence, with an optimum at pH 5.5-6. Potential for industrial biotechnology application was demonstrated in the production of a bioplastics precursor from bioderived 5-hydroxymethylfurfural.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Lucy C. Ward, Ellie Goulding, Daniel J. Rigden, Faye E. Allan, Alessandro Pellis, Harry Hatton, Georg M. Guebitz, Jesus Enrique Salcedo-Sora, Andrew J. Carnell
Summary: Mutation of the FtpM enzyme from Aspergillus fumigatus, named R166M, was reported to catalyze the quantitative conversion of bio-derived 2,5-furandicarboxylic acid (FDCA) to its dimethyl ester (FDME), the precursor of bioplastics. The AlphaFold 2 model revealed that the mutant had a highly electropositive active site, with 4 arginine residues facilitating the binding of the dicarboxylic acid over the intermediate monoester. The R166M mutation improved both binding and turnover of the monoester, allowing near quantitative conversion to the target dimethyl ester product, and showed improved activity for other diacids and monoacids.
Review
Chemistry, Multidisciplinary
Chao Wang, Rupeng Qi, Rui Wang, Zhaoqing Xu
Summary: Peptides play essential roles in biological processes and are attractive targets for therapeutic development. Incorporating unnatural amino acid residues into peptides can greatly impact their properties. Recent advancements in photoinduced radical reactions have enabled the construction of C(sp(3))-C(sp(3)) bonds under mild conditions. This study focuses on the α-C(sp(3))-H alkylation of glycine derivatives using radical-radical coupling reactions.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Emily C. Ulrich, Catherine L. Drennan
Summary: Cobalamin-dependent S-adenosyl-L-methionine radical methylases are enzymes that use a dual-cofactor system to perform challenging radical methylation reactions. They are part of a larger subgroup of enzymes that also perform difficult ring contractions and radical rearrangements. This subgroup represents a largely unexplored reservoir of diverse chemistry. This Perspective article highlights the efforts to understand the function, mechanism, and structure of TsrM, an unexpected nonradical methylase in this subgroup, and discusses recent achievements in characterizing radical methylase subgroup members.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Rahul K. Shukla, Akshay M. Nair, Chandra M. R. Volla
Summary: Recent years have witnessed the development of transition metal catalyzed C-H activation as a powerful method in organic synthesis. Allene reactivity has attracted considerable interest among synthetic chemists. Although directing group assisted C(sp(2))-H functionalization with allenes has been well studied, coupling with more challenging aliphatic C(sp(3))-H bonds remains a challenge. Here, we report a Pd(ii) catalyzed aliphatic C(sp(3))-H dienylation using allenyl acetates directed by 8-aminoquinoline. A wide range of carboxylic acids, including fatty acids and amino acids, were effectively functionalized at the beta and gamma positions to provide diversely functionalized 1,3-dienes. Preliminary mechanistic studies suggest that the success of this transformation relies on the crucial role of the base. The reaction proceeds through regioselective 2,3-migratory insertion of the allene with the alkylpalladium(ii) species followed by beta-acetoxy elimination.
Article
Chemistry, Organic
Takeshi Nanjo, Hikari Sada, Taisei Nagaya, Yuri Maruo, Yoshiji Takemoto
Summary: In this study, a cationic rhodium catalyst and methyl trifluoroborate salt were used to achieve the stereoselective formation of beta,beta-disubstituted dehydroamino acids (ΔAAs) in peptides. This method allowed the direct installation of an alkyl group on a beta-monosubstituted ΔAA in the peptide chain, leading to the successful synthesis of both isomers of dehydroisoleucine, which is an important yet usually inaccessible ΔAA.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Danilo Colombo, Alessia Albergati, Erica E. Ferrandi, Davide Tessaro, Francesco G. Gatti, Elisabetta Brenna, Daniela Monti, Fabio Parmeggiani
Summary: A new chemoenzymatic synthesis method has been developed for the preparation of weed-killing agrochemicals and chiral precursors. By carefully selecting the biocatalyst, both enantiomers of the product can be obtained in good yield, using simple and commercially available starting materials without the need for purified enzymes or chromatographic separations.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Biotechnology & Applied Microbiology
Pritam Giri, Amol D. Pagar, Mahesh D. Patil, Hyungdon Yun
Summary: This review discusses various strategies of chemical modification of enzymes, including traditional methods utilizing reactivities of canonical amino acids and emerging techniques like noncanonical amino acid-mediated 'click' chemistry and dehydroalanine (Dha)-mediated modifications, to improve functional properties and stability of industrially important biocatalysts.
BIOTECHNOLOGY ADVANCES
(2021)
Article
Chemistry, Organic
Wei Wei, Xiaodan Zhao
Summary: The carbon-carbon bond-forming cross-dehydrogenative coupling reaction using organoselenium catalysis involving a high-valent para-methoxyphenyl selenium species has been developed. This method enables the synthesis of alpha,alpha-disubstituted alpha-amino acid derivatives with excellent regioselectivities through vinyl or allylic C-H functionalization. The generality of this method has been demonstrated by the cross-coupling of an alkene with an oxindole and the direct functionalization of electron-rich arenes with azlactones.
Article
Environmental Sciences
Ankita Das, Tamalika Sanyal, Pritha Bhattacharjee
Summary: The SAM levels are reduced in individuals with arsenic induced skin lesions, and key regulatory genes in the SAM biogenesis pathway are significantly down-regulated in this group. Hypermethylation of the AS3MT promoter leads to its transcriptional repression, potentially contributing to the higher susceptibility in arsenic exposed individuals.
ENVIRONMENTAL RESEARCH
(2021)
Article
Chemistry, Applied
Palasetty Chandu, Debabrata Das, Krishna G. Ghosh, Devarajulu Sureshkumar
Summary: This study presents a visible-light mediated photoredox catalyzed decarboxylative alkylation of vinylcyclopropanes using an Ir-based photocatalyst and Cs2CO3 as a base. Long-chained alkylated derivatives were obtained in moderate to high yields under mild reaction conditions without the need for external metal co-catalysts, oxidants, or additives. Various alkyl carboxylic acids and amino acid derivatives were used as alkylating reagents to synthesize gamma,delta-unsaturated diesters and unnatural homo-allylic amino acid derivatives with excellent functional groups tolerance. The method was further validated through gram-scale synthesis and a proposed mechanism based on control experiments and quenching studies.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
James L. Galman, Fabio Parmeggiani, Lisa Seibt, William R. Birmingham, Nicholas J. Turner
Summary: In this study, an enzyme cascade system was constructed by engineering enzymes and cell strains, which could produce high-value chemicals from lignin.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
