Insights into a dual function amide oxidase/macrocyclase from lankacidin biosynthesis

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dc.identifier.uri Dorival, Jonathan Risser, Fanny Jacob, Christophe Collin, Sabrina Dräger, Gerald Paris, Cédric Chagot, Benjamin Kirschning, Andreas Gruez, Arnaud Weissman, Kira J. 2018-12-19T11:04:42Z 2018-12-19T11:04:42Z 2018
dc.identifier.citation Dorival, J.; Risser, F.; Jacob, C.; Collin, S.; Dräger, G. et al.: Insights into a dual function amide oxidase/macrocyclase from lankacidin biosynthesis. In: Nature Communications 9 (2018), Nr. 1, 3998. DOI:
dc.description.abstract Acquisition of new catalytic activity is a relatively rare evolutionary event. A striking example appears in the pathway to the antibiotic lankacidin, as a monoamine oxidase (MAO) family member, LkcE, catalyzes both an unusual amide oxidation, and a subsequent intramolecular Mannich reaction to form the polyketide macrocycle. We report evidence here for the molecular basis for this dual activity. The reaction sequence involves several essential active site residues and a conformational change likely comprising an interdomain hinge movement. These features, which have not previously been described in the MAO family, both depend on a unique dimerization mode relative to all structurally characterized members. Taken together, these data add weight to the idea that designing new multifunctional enzymes may require changes in both architecture and catalytic machinery. Encouragingly, however, our data also show LkcE to bind alternative substrates, supporting its potential utility as a general cyclization catalyst in synthetic biology. eng
dc.language.iso eng
dc.publisher London : Nature Publishing Group
dc.relation.ispartofseries Nature Communications 9 (2018), Nr. 1
dc.rights CC BY 4.0 Unported
dc.subject monoamine oxidase (MAO) eng
dc.subject LkcE eng
dc.subject catalysis eng
dc.subject.ddc 540 | Chemie ger
dc.title Insights into a dual function amide oxidase/macrocyclase from lankacidin biosynthesis eng
dc.type article
dc.type Text
dc.relation.issn 20411723
dc.bibliographicCitation.issue 1
dc.bibliographicCitation.volume 9
dc.bibliographicCitation.firstPage 3998
dc.description.version publishedVersion
tib.accessRights frei zug�nglich

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