Original Article

Extended Sequence and Functional Analysis of the Butirosin Biosynthetic Gene Cluster in Bacillus circulans SANK 72073

Fumitaka Kudo, Mario Numakura, Hideyuki Tamegai, Hideki Yamamoto, Tadashi Eguchi, Katsumi Kakinuma††

Received: February 24, 2005 / Accepted: May 10, 2005
© Japan Antibiotics Research Association

Abstract Butirosin produced by Bacillus circulans is among the clinically important 2-deoxystreptamine containing aminoglycoside antibiotics and its unique structure is found in (S)-4-amino-2-hydroxyburyric acid substituted at C-1 of 2-deoxystreptamine. Recently, the key part of the butirosin biosynthetic gene cluster has been identified from Bacillus circulans SANK 72073, however the whole gene for the biosynthesis awaited for identification. In the present study, we undertook extended analysis of the butirosin biosynthetic gene cluster and found nine additional open reading flames (ORFs), btrQ, btrR1, btrR2, btrT, btrU, btrV, btrW, btrX and orf1 in the cluster. In addition, we constructed disruption mutants of btrR1 and btrP-V, and found that the btr genes (ca. 24 Kb) between btrR1 and btrP-V are at least required for the butirosin biosynthesis.

Keywords 2-deoxystreptamine, butirosin, biosynthesis, gene cluster, gene disruption, Bacillus circulans


T. Eguchi (Corresponding author): Department of Chemistry and Materials Science, Tokyo Institute of Technology, 2-12-1, O-okayama, Meguro-ku, Tokyo 152-8551, Japan, E-mail: eguchi@cms.titech.ac.jp
F. Kudo, M. Numakura, H. Tamegai, H. Yamamoto, K. Kakinuma: Department of Chemistry, Tokyo Institute of Technology, 2-12-1, O-okayama, Meguro-ku, Tokyo 152-8551, Japan
Present address: Department of Chemistry, College of Humanities and Sciences, Nihon University, 3-25-40 Sakurajosui, Setagaya-ku, Tokyo 156-8550, Japan
†† Deceased April 1, 2005