The chromomycin CmmA acetyltransferase: a membrane-bound enzyme as a tool for increasing structural diversity of the antitumour mithramycin.
The chromomycin CmmA acetyltransferase: a membrane-bound enzyme as a tool for increasing structural diversity of the antitumour mithramycin.
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DOI：
10.1111/j.1751-7915.2010.00229.x
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发表时间：
2011-03
影响因子：
5.7
通讯作者：
Méndez C
中科院分区：
文献类型：
--
作者：
García B;González-Sabín J;Menéndez N;Braña AF;Núñez LE;Morís F;Salas JA;Méndez C
光神霉素和色霉素A3是两种结构相关的抗肿瘤化合物，它们在糖基化谱和糖的官能团取代方面不同。色霉素含有两个乙酰基，其在灰色链霉菌中的乙酰基转移酶CmmA的生物合成过程中并入。灰色的使用工程改造的S. griseus菌株产生了七种新的乙酰化mithramycins。对新生成的化合物进行了纯化，并通过MS和NMR进行了表征。这些新化合物与其母体化合物的不同之处在于存在一个、两个或三个连接在3E、4E和/或4D位置的乙酰基。所有新的光神霉素类似物在低浓度微摩尔时显示出抗肿瘤活性。一些化合物显示出对胶质母细胞瘤或胰腺肿瘤细胞的改善的活性。CmmA乙酰转移酶位于细胞膜中，并显示接受几种酰基辅酶A底物。所有这些结果都突出了CmmA作为在这些抗肿瘤化合物中创造结构多样性的工具的潜力。
Mithramycin and chromomycin A3 are two structurally related antitumour compounds, which differ in the glycosylation profiles and functional group substitutions of the sugars. Chromomycin contains two acetyl groups, which are incorporated during the biosynthesis by the acetyltransferase CmmA in Streptomyces griseus ssp. griseus. A bioconversion strategy using an engineered S. griseus strain generated seven novel acetylated mithramycins. The newly formed compounds were purified and characterized by MS and NMR. These new compounds differ from their parental compounds in the presence of one, two or three acetyl groups, attached at 3E, 4E and/or 4D positions. All new mithramycin analogues showed antitumour activity at micromolar of lower concentrations. Some of the compounds showed improved activities against glioblastoma or pancreas tumour cells. The CmmA acetyltransferase was located in the cell membrane and was shown to accept several acyl‐CoA substrates. All these results highlight the potential of CmmA as a tool to create structural diversity in these antitumour compounds.
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影响因子：
14.9
作者：
Barceló F;Scotta C;Ortiz-Lombardía M;Méndez C;Salas JA;Portugal J
通讯作者：
Portugal J
影响因子：
11.2
作者：
Chatterjee, S;Zaman, K;Ratan, RR
通讯作者：
Ratan, RR
影响因子：
3.2
作者：
Perez, Maria;Baig, Irfan;Brana, Alfredo F.;Salas, Jose A.;Rohr, Juergen;Mendez, Carmen
通讯作者：
Mendez, Carmen
影响因子：
15.9
作者：
BLUME, SW;SNYDER, RC;MILLER, DM
通讯作者：
MILLER, DM
影响因子：
--
作者：
Menéndez, N;Nur-e-Alam, M;Méndez, C
通讯作者：
Méndez, C