当前位置: X-MOL 学术J. Antibiot. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Engineered production and evaluation of 6'-deoxy-tallysomycin H-1 revealing new insights into the structure-activity relationship of the anticancer drug bleomycin.
The Journal of Antibiotics ( IF 3.3 ) Pub Date : 2017-Aug-23 , DOI: 10.1038/ja.2017.93
Dong Yang , Hindra , Liao-Bin Dong , Ivana Crnovcic , Ben Shen

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.

中文翻译:

6'-脱氧-塔利霉素H-1的工程化生产和评估揭示了对抗癌药物博来霉素的结构-活性关系的新见解。

博来霉素(BLM)是一种糖肽抗生素家族,目前在临床上与许多其他药物联合用于治疗恶性肿瘤。BLM家族的其他成员包括Tallysomycins(TLMs),phleomycins和Zorbamycin(ZBM)。我们之前克隆和表征了BLM,TLM和ZBM的生物合成基因簇。将组合生物合成策略应用于这三种生物合成机械,可以工程化生产具有独特结构特征和不同DNA裂解活性的几种BLM类似物,从而为研究BLM抗癌药物家族的构效关系(SAR)提供了绝佳的机会。现在,我们报告了一种名为6'-deoxy-TLM H-1的新型BLM-TLM-ZBM杂化代谢产物的工程生产,其由22-去甲基-BLM糖苷配基,TLMA的C-末端胺和ZBM二糖组成,通过来自ZBM生物合成基因簇的zbmGL基因在印度斯坦链球菌ΔtlmH突变菌株SB8005中的异源表达而组成。与TLM H-1和BLM A2相比,评估6'-脱氧-TLM H-1的DNA裂解活性以衡量其潜在的抗癌活性,揭示了对BLM系列抗癌药物SAR的新见解。 《抗生素杂志》提前在线发布,2017年8月23日; doi:10.1038 / ja.2017.93。与TLM H-1和BLM A2相比,-deoxy-TLM H-1作为其潜在抗癌活性的量度,揭示了对BLM系列抗癌药的SAR的新见解。《抗生素杂志》在线上发表,8月23日2017; doi:10.1038 / ja.2017.93。与TLM H-1和BLM A2相比,-deoxy-TLM H-1作为其潜在抗癌活性的量度,揭示了对BLM系列抗癌药的SAR的新见解。《抗生素杂志》在线上发表,8月23日2017; doi:10.1038 / ja.2017.93。
更新日期:2017-08-23
down
wechat
bug