Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation

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dc.contributor.authorJ W Park-
dc.contributor.authorS R Park-
dc.contributor.authorK K Nepal-
dc.contributor.authorA R Han-
dc.contributor.authorY H Ban-
dc.contributor.authorY J Yoo-
dc.contributor.authorE J Kim-
dc.contributor.authorE M Kim-
dc.contributor.authorDoo-Il Kim-
dc.contributor.authorJ K Sohng-
dc.contributor.authorY J Yoon-
dc.date.accessioned2017-04-19T09:25:57Z-
dc.date.available2017-04-19T09:25:57Z-
dc.date.issued2011-
dc.identifier.issn1552-4450-
dc.identifier.uri10.1038/nchembio.671ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/10414-
dc.description.abstractKanamycin is one of the most widely used antibiotics, yet its biosynthetic pathway remains unclear. Current proposals suggest that the kanamycin biosynthetic products are linearly related via single enzymatic transformations. To explore this system, we have reconstructed the entire biosynthetic pathway through the heterologous expression of combinations of putative biosynthetic genes from Streptomyces kanamyceticus in the non-aminoglycoside-producing Streptomyces venezuelae. Unexpectedly, we discovered that the biosynthetic pathway contains an early branch point, governed by the substrate promiscuity of a glycosyltransferase, that leads to the formation of two parallel pathways in which early intermediates are further modified. Glycosyltransferase exchange can alter flux through these two parallel pathways, and the addition of other biosynthetic enzymes can be used to synthesize known and new highly active antibiotics. These results complete our understanding of kanamycin biosynthesis and demonstrate the potential of pathway engineering for direct in vivo production of clinically useful antibiotics and more robust aminoglycosides.-
dc.publisherSpringer-Nature Pub Group-
dc.titleDiscovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation-
dc.title.alternativeDiscovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation-
dc.typeArticle-
dc.citation.titleNature Chemical Biology-
dc.citation.number11-
dc.citation.endPage852-
dc.citation.startPage843-
dc.citation.volume7-
dc.contributor.affiliatedAuthorDoo-Il Kim-
dc.contributor.alternativeName박제원-
dc.contributor.alternativeName박성렬-
dc.contributor.alternativeNameNepal-
dc.contributor.alternativeName한아름-
dc.contributor.alternativeName반연희-
dc.contributor.alternativeName유영지-
dc.contributor.alternativeName김은지-
dc.contributor.alternativeName김의민-
dc.contributor.alternativeName김두일-
dc.contributor.alternativeName송재경-
dc.contributor.alternativeName윤여준-
dc.identifier.bibliographicCitationNature Chemical Biology, vol. 7, no. 11, pp. 843-852-
dc.identifier.doi10.1038/nchembio.671-
dc.description.journalClassY-
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