Bleomycin Potency Boost | Chemical & Engineering News
Volume 90 Issue 32 | p. 35 | Concentrates
Issue Date: August 6, 2012

Bleomycin Potency Boost

Combinatorial biosynthesis produces analog with uniquely high activity
Department: Science & Technology
News Channels: Biological SCENE, JACS In C&EN
Keywords: bleomycin, combinatorial biosynthesis

Bleomycins are approved drugs used in cocktails with other medicines for conditions such as testicular cancer, but they have serious side effects, including lung inflammation. Now, a team has used combinator­ial biosynthesis (genetic engineering of biosynthetic pathways) to create a designed bleomycin with uniquely high potency, which could lead to anticancer agents with improved side-effect profiles. The work was carried out by Yanwen Duan of Hunan Engineering Research Center of Combinatorial Biosynthesis & Natural Product Drug Discovery, in China; Ben Shen of Scripps Research Institute; and coworkers (J. Am. Chem. Soc., DOI: 10.1021/ja3056535). The researchers previously cloned and characterized the biosynthetic gene clusters that bacteria use to produce bleomycins. By analyzing the clusters, they were able to devise a plan for engineering analogs with potentially higher activity, and they succeeded by creating 6′-deoxybleomycin Z, the most potent bleomycin analog to date. The analog could lead to “new bleomycin chemotherapy regimens with reduced dosage, thereby lessening dose-limiting side effects and the incidence of lung toxicity,” Shen says.

 
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