Please use this identifier to cite or link to this item: https://doi.org/10.1002/anie.201307404
Title: Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis
Authors: Hotta, K. 
Keegan, R.M.
Ranganathan, S.
Fang, M.
Bibby, J.
Winn, M.D.
Sato, M.
Lian, M.
Watanabe, K.
Rigden, D.J.
Kim, C.-Y. 
Keywords: biosynthesis
disulfides
peptides
thioacetals
transferases
Issue Date: 2014
Source: Hotta, K., Keegan, R.M., Ranganathan, S., Fang, M., Bibby, J., Winn, M.D., Sato, M., Lian, M., Watanabe, K., Rigden, D.J., Kim, C.-Y. (2014). Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis. Angewandte Chemie - International Edition 53 (3) : 824-828. ScholarBank@NUS Repository. https://doi.org/10.1002/anie.201307404
Abstract: Echinomycin is a nonribosomal depsipeptide natural product with a range of interesting bioactivities that make it an important target for drug discovery and development. It contains a thioacetal bridge, a unique chemical motif derived from the disulfide bond of its precursor antibiotic triostin A by the action of an S-adenosyl-L-methionine-dependent methyltransferase, Ecm18. The crystal structure of Ecm18 in complex with its reaction products S-adenosyl-L-homocysteine and echinomycin was determined at 1.50 Å resolution. Phasing was achieved using a new molecular replacement package called AMPLE, which automatically derives search models from structure predictions based on ab initio protein modelling. Structural analysis indicates that a combination of proximity effects, medium effects, and catalysis by strain drives the unique transformation of the disulfide bond into the thioacetal linkage. Disulfide to thioacetal: The S-adenosyl-L-methionine (SAM)-dependent methyltransferase Ecm 18 converts the disulfide bond of triostin A into a thioacetal linkage to form echinomycin. The 1.50 Å crystal structure of Ecm 18 in complex with its reaction products S-adenosyl-L-homocysteine (SAH) and echinomycin provides insight into how Ecm 18 catalyzes this unusual transformation. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Source Title: Angewandte Chemie - International Edition
URI: http://scholarbank.nus.edu.sg/handle/10635/100338
ISSN: 14337851
DOI: 10.1002/anie.201307404
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