Biosynthesis of 3′-Deoxy-carbamoylkanamycin C in a Streptomyces tenebrarius Mutant Strain by tacB Gene Disruption

Abstract

Streptomyces tenebrarius H6 mainly produces three kinds of antibiotics: apramycin, carbamoyltobramycin and some carbamoylkanamycin B. In our present study, a dehydrogenase gene tacB in the tobramycin biosynthetic gene cluster was disrupted by in-frame deletion. The result of TLC bio-autograph analysis demonstrated the disruption mutant strain produced apramycin and a new antibiotic. The new antibiotic was identified as 3′-deoxy-carbamoylkanamycin C by MS and NMR analysis after isolation and purification. The disruption mutant was restored to produce carbamoyltobramycin in a complementation experiment by the intact tacB gene. Our studies suggested that the tacB gene encodes a 6′-dehydrogenase, which reduces the 6′-hydroxyl group of paromamine to a keto group, thus facilitating the transfer of an aminogroup to form neamine. This study is the first report on the generation of a tobramycin derivative by gene engineering, and will contribute to clarify the complete biosynthetic pathway of tobramycin.

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Correspondence to Huanzhang Xia.

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Yu, Y., Hou, X., Ni, X. et al. Biosynthesis of 3′-Deoxy-carbamoylkanamycin C in a Streptomyces tenebrarius Mutant Strain by tacB Gene Disruption. J Antibiot 61, 63–69 (2008). https://doi.org/10.1038/ja.2008.111

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Keywords

  • Streptomyces tenebrarius
  • in-frame deletion
  • complementation
  • 6′-dehydrogenase
  • 3′-deoxy-carbamoylkanamycin C

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