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Antimicrobial Agents and Chemotherapy, November 2000, p. 3040-3048, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Identification of the Coumermycin A1
Biosynthetic Gene Cluster of Streptomyces rishiriensis
DSM 40489
Zhao-Xin
Wang,
Shu-Ming
Li, and
Lutz
Heide*
Pharmazeutische Biologie, Pharmazeutisches
Institut, Eberhard-Karls-Universität Tübingen, 72076 Tübingen, Germany
Received 24 April 2000/Returned for modification 10 July
2000/Accepted 10 August 2000
The biosynthetic gene cluster of the aminocoumarin antibiotic
coumermycin A1 was cloned by screening of a cosmid library
of Streptomyces rishiriensis DSM 40489 with heterologous
probes from a dTDP-glucose 4,6-dehydratase gene, involved in
deoxysugar biosynthesis, and from the aminocoumarin resistance gyrase
gene gyrBr. Sequence analysis of a 30.8-kb
region upstream of gyrBr revealed the presence
of 28 complete open reading frames (ORFs). Fifteen of the identified
ORFs showed, on average, 84% identity to corresponding ORFs in the
biosynthetic gene cluster of novobiocin, another aminocoumarin
antibiotic. Possible functions of 17 ORFs in the biosynthesis of
coumermycin A1 could be assigned by comparison with sequences in GenBank. Experimental proof for the function of the
identified gene cluster was provided by an insertional gene
inactivation experiment, which resulted in an abolishment of
coumermycin A1 production.
*
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, November 2000, p. 3040-3048, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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