ArticleThe Journal of antibiotics2017
Engineered production and evaluation of 6'-deoxy-tallysomycin H-1 revealing new insights into the structure-activity relationship of the anticancer drug bleomycin.
Article in The Journal of antibiotics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bleomycins (BLMs), a family of glycopeptide antibiotics, are currently used clinically in combination with a number of other agents for the treatment of malignant tumors. Other members of the BLM family include tallysomycins (TLMs), phleomycins and zorbamycin (ZBM). We previously cloned and characterized the biosynthetic gene clusters for BLMs, TLMs and ZBM. Applications of combinatorial biosynthesis strategies to the three biosynthetic machineries enabled the engineered production of several BLM analogs with unique structural characteristics and varying DNA cleavage activities, thereby providing an outstanding opportunity to study the structure-activity relationship (SAR) for the BLM family of anticancer drugs. We now report the engineered production of a new BLM-TLM-ZBM hybrid metabolite, named 6'-deoxy-TLM H-1, which consists of the 22-desmethyl-BLM aglycone, the TLM A C-terminal amine and the ZBM disaccharide, by heterologous expression of the zbmGL genes from the ZBM biosynthetic gene cluster in the Streptoalloteichus hindustanus ΔtlmH mutant strain SB8005. Evaluation of the DNA cleavage activities of 6'-deoxy-TLM H-1 as a measurement for its potential anticancer activity, in comparison with TLM H-1 and BLM A2, reveals new insight into the SAR of BLM family of anticancer drugs.The Journal of Antibiotics advance online publication, 23 August 2017; doi:10.1038/ja.2017.93.
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