Functional Characterization of ttmM Unveils New Tautomycin Analogs and Insight into Tautomycin Biosynthesis and Activity
Functional Characterization of ttmM Unveils New Tautomycin Analogs and Insight into Tautomycin Biosynthesis and Activity
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DOI：
10.1021/ol900293j
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发表时间：
2009-04-02
期刊：
影响因子：
5.2
通讯作者：
Shen, Ben
中科院分区：
文献类型：
--
作者：
Ju, Jianhua;Li, Wenli;Shen, Ben
互变霉素（TTM）是一种有效的蛋白磷酸酶（PP）抑制剂，其生物合成基因簇最近已被鉴定。失活ttmM（其编码推定的C3'羟化酶）得到突变体SB 6005，其积累三个新的3'-脱羟基TTM类似物，支持TtmM的功能和先前提出的TTM生物合成的线性途径。生物测定揭示了C3' OH部分在PP抑制中的重要性，并且PP抑制不是驱动TTM诱导的细胞死亡的唯一机制。
The biosynthetic gene cluster for tautomycin (TTM), a potent protein phosphatase (PP) inhibitor has recently been characterized. Inactivation of ttmM, which encodes a putative C3' hydroxylase, afforded mutant SB6005 which accumulated three new 3'-deshydroxy TTM analogs, supporting the function of TtmM and the previously proposed linear pathway for TTM biosynthesis. Bioassays reveal the importance of the C3' OH moiety in PP inhibition and that PP inhibition is not the exclusive mechanism driving TTM-induced cell death.