An Unusual Flavin-Dependent Halogenase from the Metagenome of the Marine Sponge Theonella swinhoei WA

• Published in: ACS chemical biology Vol. 12; no. 5; pp. 1281 - 1287
• Main Authors: Smith, Duncan R. M, Uria, Agustinus R, Helfrich, Eric J. N, Milbredt, Daniela, van Pée, Karl-Heinz, Piel, Jörn, Goss, Rebecca J. M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19-05-2017
• Subjects: Amides - metabolism; Animals; Bacteria - genetics; Bacteria - metabolism; Biosynthetic Pathways; Flavins; Halogenation; Hydrolases - metabolism; Metagenome - genetics; Multigene Family; Porifera - microbiology; Theonella - microbiology
• ISSN: 1554-8929; 1554-8937
• DOI: 10.1021/acschembio.6b01115

Uncultured bacteria from sponges have been demonstrated to be responsible for the generation of many potent, bioactive natural products including halogenated metabolites. The identification of gene clusters from the metagenomes of such bacterial communities enables the discovery of enzymes that mediate new and useful chemistries and allows insight to be gained into the biogenesis of potentially pharmacologically important natural products. Here we report a new pathway to the keramamides (krm); the first functional evidence for the existence of a distinct producer in the Theonella swinhoei WA chemotype is revealed, and a key enzyme on the pathway, a unique flavin-dependent halogenase with a broad substrate specificity, with potential as a useful new biocatalytic tool, is described.