Taxol biosynthesis: Identification and characterization of two acetyl CoA:taxoid-O-acetyl transferases that divert pathway flux away from Taxol production.
Taxol biosynthesis: Identification and characterization of two acetyl CoA:taxoid-O-acetyl transferases that divert pathway flux away from Taxol production.
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紫杉醇生物合成：两种乙酰COA的识别和表征：将通路途径转移到紫杉醇产量的途径途径。
DOI：
10.1016/j.abb.2009.05.018
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发表时间：
2009-07-15
影响因子：
3.9
通讯作者：
Croteau RB
中科院分区：
文献类型：
--
作者：
Hampel D;Mau CJ;Croteau RB
从先前分离的红豆杉酰基/芳香基转移酶cDNA克隆家族中获得了两个编码taxoid- o -乙酰基转移酶的cDNA （tax9和tax14）。重组酶催化taxadi烯-5α、13α-二乙酰氧基-9α、10β-二醇的乙酰化，分别生成taxadi烯-5α、10β、13α-三乙酰氧基-9α-醇和taxadi烯-5α、9α、13α-三乙酰氧基-10β-醇，然后作为底物进行最后的乙酰化步骤，生成taxusin， taxusin是红豆杉的一个重要的侧通路代谢产物。这两种酶都不能使紫杉素多元醇的5α-或13α-羟基乙酰化，这表明紫杉素的过乙酰化需要事先的酰化。对两种酶进行了动力学表征，发现乙酰化的区域选择性随ph值的变化而变化。与其他类杉酰基转移酶的序列比较证实了该酶的一级结构在类杉代谢中的作用不大。与先前发现的参与紫杉醇生产的乙酰转移酶不同，这两种酶似乎只作用于部分乙酰化的类紫杉醇，将紫杉醇途径转移到侧通路代谢产物。
Two cDNAs encoding taxoid-O-acetyl transferases (TAX 9 and TAX 14) were obtained from a previously isolated family of Taxus acyl/aroyl transferase cDNA clones. The recombinant enzymes catalyze the acetylation of taxadien-5α,13α-diacetoxy-9α,10β-diol to generate taxadien-5α,10β,13α-tri-acetoxy-9α-ol and taxadien-5α,9α,13α-triacetoxy-10β-ol, respectively, both of which then serve as substrates for a final acetylation step to yield taxusin, a prominent side route metabolite of Taxus. Neither enzyme acetylate the 5α- or the 13α-hydroxyls of taxoid polyols, indicating that prior acylations is required for efficient peracetylation to taxusin. Both enzymes were kinetically characterized, and the regioselectivity of acetylation was shown to vary with pH. Sequence comparison with other taxoid acyl transferases confirmed that primary structure of this enzyme type reveals little about function in taxoid metabolism. Unlike previously identified acetyl transferases involved in Taxol production, these two enzymes appear to act exclusively on partially acetylated taxoid polyols to divert the Taxol pathway to side-route metabolites.
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影响因子：
--
作者：
Chau, M;Jennewein, S;Croteau, R
通讯作者：
Croteau, R
影响因子：
7.7
作者：
Kaspera, Rudiger;Croteau, Rodney
通讯作者：
Croteau, Rodney
影响因子：
4.8
作者：
KOEPP, AE;HEZARI, M;CROTEAU, R
通讯作者：
CROTEAU, R
影响因子：
--
作者：
Jennewein, S;Long, RM;Croteau, R
通讯作者：
Croteau, R
影响因子：
3.9
作者：
Chau, MD;Walker, K;Croteau, R
通讯作者：
Croteau, R