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Applied and Environmental Microbiology, January 2005, p. 400-406, Vol. 71, No. 1
0099-2240/05/$08.00+0 doi:10.1128/AEM.71.1.400-406.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Institut für Pharmazeutische Wissenschaften, Pharmazeutische Biologie und Biotechnologie, Albert-Ludwigs-Universität Freiburg, Freiburg,1 Institut für Organische Chemie und Biochemie II, Technische Universität München, Munich,2 Combinature Biopharm AG, Berlin, Germany3
Received 1 June 2004/ Accepted 23 August 2004
Eurekanate belongs to the important class of branched-chain carbohydrates present in a wide variety of natural sources. It is a component of avilamycin A, a potent inhibitor of bacterial protein synthesis targeting the 50S ribosomal subunit. The present work provides experimental proof for the function of two genes of the avilamycin biosynthetic gene cluster, aviB1 and aviO2, that are both involved in avilamycin structure modification. The functions of both genes were identified by gene inactivation experiments and nuclear magnetic resonance analyses of extracts produced by the mutants. We suggest that both AviO2 and AviB1 are involved in the biosynthesis of eurekanate within avilamycin biosynthesis. Moreover, two other genes (aviO1 and aviO3) have been inactivated, resulting in a breakdown of avilamycin production in the mutants ITO1 and ITO3, which clearly shows the essential role of both enzymes in avilamycin biosynthesis. The exact functions of both aviO1 and aviO3 remained unknown.
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