0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      One-pot chemoenzymatic syntheses of non-canonical amino acids

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

           

          Despite their prevalent use in drug discovery and protein biochemistry, non-canonical amino acids are still challenging to synthesize through purely chemical means. In recent years, biocatalysis has emerged as a transformative paradigm for small-molecule synthesis. One strategy to further empower biocatalysis is to use it in combination with modern chemical reactions and take advantage of the strengths of each method to enable access to challenging structural motifs that were previously unattainable using each method alone. In this Mini-Review, we highlight several recent case studies that feature the synergistic use of chemical and enzymatic transformations in one pot to synthesize novel non-canonical amino acids.

          One-Sentence Summary

          This Mini-Review highlights several recent case studies that feature the synergistic use of chemical and enzymatic transformations in one pot to synthesize novel non-canonical amino acids.

          Graphical Abstract

          Graphical Abstract

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          AMA overcomes antibiotic resistance by NDM and VIM metallo-β-lactamases

          The emergence and spread of carbapenem-resistant Gram-negative pathogens is a global public health problem. The acquisition of metallo-β-lactamases (MBLs) such as NDM-1 is a principle contributor to the emergence of carbapenem-resistant Gram-negative pathogens that threatens the use of penicillin, cephalosporin, and carbapenem antibiotics to treat infections. So far a clinical inhibitor of MBLs that could reverse resistance and re-sensitize resistant Gram-negative pathogens to carbapenems does not exist. Here we have identified a fungal natural product, aspergillomarasmine A (AMA) that is a rapid and potent inhibitor of the NDM-1 enzyme and another clinically relevant MBL, VIM-2. AMA also fully restored the activity of meropenem against Enterobacteriaceae, Acinetobacter spp. and Pseudomonas spp. possessing either VIM or NDM-type alleles. In mice infected with NDM-1-expressing Klebsiella pneumoniae, AMA efficiently restored meropenem activity, demonstrating that a combination of AMA and a carbapenem antibiotic has therapeutic potential to address the clinical challenge of MBL positive carbapenem-resistant Gram-negative pathogens.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Catalytic asymmetric synthesis of alpha-amino acids.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Photoexcitation of flavoenzymes enables a stereoselective radical cyclization

              Photoexcitation is a common strategy for initiating radical reactions in chemical synthesis. We found that photoexcitation of flavin-dependent “ene”-reductases changes their catalytic function, enabling these enzymes to promote an asymmetric radical cyclization. This reactivity enables the construction of five-, six-, seven-, and eight-membered lactams with stereochemical preference conferred by the enzyme active site. After formation of a prochiral radical, the enzyme guides the delivery of a hydrogen atom from flavin—a challenging feat for small-molecule chemical reagents. The initial electron transfer occurs through direct excitation of an electron donor-acceptor complex that forms between the substrate and the reduced flavin cofactor within the enzyme active site. Photoexcitation of promiscuous flavoenzymes has thus furnished a previously unknown biocatalytic reaction.
                Bookmark

                Author and article information

                Contributors
                Journal
                J Ind Microbiol Biotechnol
                J Ind Microbiol Biotechnol
                jimb
                Journal of Industrial Microbiology & Biotechnology
                Oxford University Press
                1367-5435
                1476-5535
                2024
                25 January 2024
                25 January 2024
                : 51
                : kuae005
                Affiliations
                De partment of Chemistry, BioScience Research Collaborative, Rice University , Houston, TX 77005, USA
                De partment of Chemistry, BioScience Research Collaborative, Rice University , Houston, TX 77005, USA
                De partment of Chemistry, BioScience Research Collaborative, Rice University , Houston, TX 77005, USA
                Author notes
                Correspondence should be addressed to: Hans Renata at hr28@ 123456rice.edu

                Equal contribution.

                Author information
                https://orcid.org/0000-0003-2468-2328
                Article
                kuae005
                10.1093/jimb/kuae005
                10853765
                38271597
                06cfec1b-6dcf-46ab-8b03-99d1287aa6fa
                © The Author(s) 2024. Published by Oxford University Press on behalf of Society of Industrial Microbiology and Biotechnology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 28 November 2023
                : 24 January 2024
                : 09 February 2024
                Page count
                Pages: 8
                Funding
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Award ID: R35 GM128895
                Categories
                Mini-Review
                Biocatalysis
                Jimb/1
                AcademicSubjects/SCI01150
                AcademicSubjects/SCI00540

                Biotechnology
                non-canonical amino acid,chemoenzymatic,biocatalysis,oxidation,plp
                Biotechnology
                non-canonical amino acid, chemoenzymatic, biocatalysis, oxidation, plp

                Comments

                Comment on this article