Pathway Engineering of Anthracyclines: Blazing Trails in Natural Product Glycodiversification.

Pathway Engineering of Anthracyclines: Blazing Trails in Natural Product Glycodiversification.
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蒽环类药物的通路工程:天然产物糖多样化的创新。

DOI:
10.1021/acs.joc.0c01863
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发表时间:
2020-10-02
期刊:
The Journal of organic chemistry
影响因子:
--
通讯作者:
Nybo SE
Nybo SE
中科院分区:
其他
文献类型:
--
作者:
Brown KV;Wandi BN;Metsä-Ketelä M;Nybo SE

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蒽环类药物是一种结构多样的抗癌天然产物,可与DNA结合并毒害癌细胞中的拓扑异构酶II - DNA复合物。脱氧糖功能的合理修饰对合成具有改善效力的药物特别有利。糖基转移酶和脱氧糖合成酶的组合生物合成是合成含糖多样化的蒽环类药物所不可缺少的。本文综述了糖基转移酶结构生物学和位点定向诱变、途径工程和脱氧糖组合生物合成方面的最新进展,重点是“新自然”蒽环类药物类似物的产生。
The anthracyclines are structurally diverse anticancer natural products that bind to DNA and poison the topoisomerase II – DNA complex in cancer cells. Rational modifications in the deoxysugar functionality are especially advantageous for synthesizing drugs with improved potency. Combinatorial biosynthesis of glycosyltransferases and deoxysugar synthesis enzymes is indispensable for the generation of glycodiversified anthracyclines. This Synopsis considers recent advances in glycosyltransferase structural biology and site-directed mutagenesis, pathway engineering, and deoxysugar combinatorial biosynthesis with a focus on the generation of “new-to-nature” anthracycline analogs.
DOI: 10.1021/np020112z
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