scholarly journals C–C bond forming radical SAM enzymes involved in the construction of carbon skeletons of cofactors and natural products

2018 ◽  
Vol 35 (7) ◽  
pp. 660-694 ◽  
Author(s):  
Kenichi Yokoyama ◽  
Edward A. Lilla
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Radical Sam ◽  
Radical Sam Enzymes ◽  
Bond Forming ◽  
Cofactor Biosynthesis

An emerging group of radical SAM enzymes that catalyze C–C bond formations in natural product and cofactor biosynthesis are discussed.

scholarly journals Radical SAM Enzymes and Ribosomally‐Synthesized and Post‐translationally Modified Peptides: A Growing Importance in the Microbiomes

2021 ◽  
Vol 9 ◽  
Author(s):  
Alhosna Benjdia ◽  
Olivier Berteau
Keyword(s):  
Natural Products ◽  
Posttranslational Modifications ◽  
High Throughput Screening ◽  
Combinatorial Libraries ◽  
Special Focus ◽  
Radical Sam ◽  
Radical Sam Enzymes ◽  
Recent Developments ◽  
Modified Peptides ◽  
Drug Leads

To face the current antibiotic resistance crisis, novel strategies are urgently required. Indeed, in the last 30 years, despite considerable efforts involving notably high-throughput screening and combinatorial libraries, only few antibiotics have been launched to the market. Natural products have markedly contributed to the discovery of novel antibiotics, chemistry and drug leads, with more than half anti-infective and anticancer drugs approved by the FDA being of natural origin or inspired by natural products. Among them, thanks to their modular structure and simple biosynthetic logic, ribosomally synthesized and posttranslationally modified peptides (RiPPs) are promising scaffolds. In addition, recent studies have highlighted the pivotal role of RiPPs in the human microbiota which remains an untapped source of natural products. In this review, we report on recent developments in radical SAM enzymology and how these unique biocatalysts have been shown to install complex and sometimes unprecedented posttranslational modifications in RiPPs with a special focus on microbiome derived enzymes.

scholarly journals Radical SAM enzymes in the biosynthesis of sugar-containing natural products

2012 ◽  
Vol 1824 (11) ◽  
pp. 1231-1244 ◽  
Author(s):  
Mark W. Ruszczycky ◽  
Yasushi Ogasawara ◽  
Hung-wen Liu
Keyword(s):  
Natural Products ◽  
Radical Sam ◽  
Radical Sam Enzymes

New Role for Radical SAM Enzymes in the Biosynthesis of Thio(seleno)oxazole RiPP Natural Products

Biochemistry ◽  
2021 ◽  
Author(s):  
Julia K. Lewis ◽  
Andrew S. Jochimsen ◽  
Sarah J. Lefave ◽  
Anthony P. Young ◽  
William M. Kincannon ◽  
...  
Keyword(s):  
Natural Products ◽  
Radical Sam ◽  
Radical Sam Enzymes

Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A

2018 ◽  
Author(s):  
Jonathan J. Mills ◽  
Kaylib R. Robinson ◽  
Troy E. Zehnder ◽  
Joshua G. Pierce
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Mechanism Of Action ◽  
Marine Natural Products ◽  
Biological Evaluation ◽  
Lead Compounds ◽  
Follow Up Studies ◽  
Initial Resistance ◽  
Synthesis And Biological Evaluation

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

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