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One Enzyme To Build Them All : Ring-Size Engineered Siderophores Inhibit the Swarming Motility of Vibrio

One Enzyme To Build Them All : Ring-Size Engineered Siderophores Inhibit the Swarming Motility of Vibrio

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RÜTSCHLIN, Sina, Sandra GUNESCH, Thomas BÖTTCHER, 2018. One Enzyme To Build Them All : Ring-Size Engineered Siderophores Inhibit the Swarming Motility of Vibrio. In: ACS Chemical Biology. 13(5), pp. 1153-1158. ISSN 1554-8929. eISSN 1554-8937. Available under: doi: 10.1021/acschembio.8b00084

@article{Rutschlin2018-05-18Enzym-42552, title={One Enzyme To Build Them All : Ring-Size Engineered Siderophores Inhibit the Swarming Motility of Vibrio}, year={2018}, doi={10.1021/acschembio.8b00084}, number={5}, volume={13}, issn={1554-8929}, journal={ACS Chemical Biology}, pages={1153--1158}, author={Rütschlin, Sina and Gunesch, Sandra and Böttcher, Thomas} }

2018-06-13T07:10:19Z One Enzyme To Build Them All : Ring-Size Engineered Siderophores Inhibit the Swarming Motility of Vibrio Bacteria compete for ferric iron by producing siderophores, and some microbes engage in piracy by scavenging siderophores of their competitors. The macrocyclic hydroxamate siderophore avaroferrin of Shewanella algae inhibits swarming of Vibrio alginolyticus by evading this piracy. Avaroferrin, as well as related putrebactin and bisucaberin, are produced by the IucC-like synthetases AvbD, PubC, and BibC<sup>C</sup>. Here, we have established that they are capable of synthesizing not only their native product but also other siderophores. Exploiting this relaxed substrate specificity by synthetic precursors generated 15 different ring-size engineered macrocycles ranging from 18- to 28-membered rings, indicating unprecedented biosynthetic flexibility of the enzymes. Two of the novel siderophores could be obtained in larger quantities by precursor-directed biosynthesis in S. algae. Both inhibited swarming motility of Vibrio and, similar to avaroferrin, the most active one exhibited a heterodimeric architecture. Our results demonstrate the impact of minor structural changes on biological activity, which may trigger the evolution of siderophore diversity. Böttcher, Thomas Rütschlin, Sina Böttcher, Thomas 2018-05-18 eng 2018-06-13T07:10:19Z Gunesch, Sandra Gunesch, Sandra Rütschlin, Sina

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