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Antimicrobial Agents and Chemotherapy, May 2000, p. 1214-1222, Vol. 44, No. 5
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Identification of the Novobiocin Biosynthetic Gene Cluster of Streptomyces spheroides NCIB 11891

Marion Steffensky, Agnes Mühlenweg, Zhao-Xin Wang, Shu-Ming Li, and Lutz Heide*

Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard-Karls-Universität Tübingen, 72076 Tübingen, Germany

Received 12 August 1999/Returned for modification 9 December 1999/Accepted 29 January 2000

The novobiocin biosynthetic gene cluster from Streptomyces spheroides NCIB 11891 was cloned by using homologous deoxynucleoside diphosphate (dNDP)-glucose 4,6-dehydratase gene fragments as probes. Double-stranded sequencing of 25.6 kb revealed the presence of 23 putative open reading frames (ORFs), including the gene for novobiocin resistance, gyrBr, and at least 11 further ORFs to which a possible role in novobiocin biosynthesis could be assigned. An insertional inactivation experiment with a dNDP-glucose 4,6-dehydratase fragment resulted in abolishment of novobiocin production, since biosynthesis of the deoxysugar moiety of novobiocin was blocked. Heterologous expression of a key enzyme of novobiocin biosynthesis, i.e., novobiocic acid synthetase, in Streptomyces lividans TK24 further confirmed the involvement of the analyzed genes in the biosynthesis of the antibiotic.

* Corresponding author. Mailing address: Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany. Phone: 49-7071-29-72460. Fax: 49-7071-29-5250. E-mail: heide{at}uni-tuebingen.de.

Antimicrobial Agents and Chemotherapy, May 2000, p. 1214-1222, Vol. 44, No. 5
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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