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Identification of the Enzymes Mediating the Maturation of the Seryl-tRNA Synthetase Inhibitor SB-217452 during the Biosynthesis of Albomycins |
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| Authors: | Richiro Ushimaru Zhang Chen Houyuan Zhao Po-hsun Fan Prof?Dr Hung-wen Liu |
| Institution: | 1. Department of Chemistry, and Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX, 78712 USA
These authors contributed equally to this work.;2. Department of Chemistry, and Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX, 78712 USA |
| Abstract: | Albomycin δ2 is a sulfur-containing sideromycin natural product that shows potent antibacterial activity against clinically important pathogens. The l -serine-thioheptose dipeptide partial structure, known as SB-217452, has been found to be the active seryl-tRNA synthetase inhibitor component of albomycin δ2. Herein, it is demonstrated that AbmF catalyzes condensation between the 6′-amino-4′-thionucleoside with the d -ribo configuration and seryl-adenylate supplied by the serine adenylation activity of AbmK. Formation of the dipeptide is followed by C3′-epimerization to produce SB-217452 with the d -xylo configuration, which is catalyzed by the radical S-adenosyl-l -methionine enzyme AbmJ. Gene deletion suggests that AbmC is involved in peptide assembly linking SB-217452 with the siderophore moiety. This study establishes how the albomycin biosynthetic machinery generates its antimicrobial component SB-217452. |
| Keywords: | Albomycin Amidbindungsbildung Biosynthese Epimerisierung Radikalische S-Adenosyl-l-Methionin-Enzyme |