Transketolase Activity in the Formation of the Azinomycin Azabicycle Moiety
Transketolase Activity in the Formation of the Azinomycin Azabicycle Moiety
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阿嗪霉素氮杂双环部分形成中的转酮酶活性
DOI：
10.1021/acs.biochem.9b00477
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发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Watanabe, Coran M.
中科院分区：
文献类型：
--
作者：
Washburn, Lauren A.;Foley, Brendan;Martinez, Flor;Lee, Rachel P.;Pryor, Kendall;Rimes, Emily;Watanabe, Coran M.
阿奇霉素的生物合成涉及谷氨酸转化为氮丙啶并[1，2-a]吡咯烷部分，其与环氧化物部分一起赋予这些药剂抗癌活性。氮杂双环戊二烯的形成机制是复杂的，涉及至少14个酶促步骤。前期研究发现N-乙酰谷氨酸5-半醛是谷氨酸氨基端保护和γ-羧酸还原的关键中间体。本研究报告了一种硫胺素依赖性转酮醇酶的开创性发现，该酶负责形成2-乙酰氨基-5，6-二羟基-6-氧代庚酸，该庚酸负责完成氮杂双环戊二烯部分的碳框架所需的两个碳延伸。
The biosynthesis of the azinomycins involves the conversion of glutamic acid to an aziridino[1,2-a]pyrrolidine moiety, which together with the epoxide moiety imparts anticancer activity to these agents. The mechanism of azabicycle formation is complex and involves at least 14 enzymatic steps. Previous research has identifiedN-acetyl-glutamate 5-semialdehyde as a key intermediate, which originates from protection of the amino terminus of glutamic acid and subsequent reduction of the γ-carboxylate. This study reports on the seminal discovery of a thiamin-dependent transketolase responsible for the formation of 2-acetamido-5,6-dihydroxy-6-oxoheptanoic acid, which accounts for the two-carbon extension needed to complete the carbon framework of the azabicycle moiety.