Concentrated biosynthesis of tobramycin by genetically engineered Streptomyces tenebrarius.

Abstract

Tobramycin is an important broad spectrum aminoglycoside antibiotic widely used against severe Gram-negative bacterial infections. It is produced by base-catalyzed hydrolysis of carbamoyltobramycin (CTB) generated by S. tenebrarius. We herein report the construction of a genetically engineered S. tenebrarius for direct fermentative production of tobramycin by disruption of aprK and tobZ. A unique putative NDP-octodiose synthase gene aprK was disrupted to optimize the production of CTB, resulting in the blocking of apramycin biosynthesis and the obvious increase in CTB production of aprK disruption mutant S. tenebrarius ST316. Additional mutation on the carbamoyltransferase gene tobZ in S. tenebrarius ST316 generated a strain ST318 that produces tobramycin as a single metabolite. ST318 could be used for industrial fermentative production of tobramycin.

• Authors: Jianping Xiao, Hui Li, Shuping Wen, Wenrong Hong
• Journal: The Journal of general and applied microbiology (J Gen Appl Microbiol) Vol. 60 Issue 6 Pg. 256-61 ( 2014) ISSN: 1349-8037 [Electronic] Japan
• PMID: 25742977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Tobramycin

Topics

• Bacterial Proteins (genetics)
• Biosynthetic Pathways (genetics)
• Fermentation
• Gene Knockout Techniques
• Metabolic Engineering
• Streptomyces (genetics, metabolism)
• Tobramycin (biosynthesis)