解码氨甲酰多氧草氨酸生物合成：揭示其途径中含有乙酰化循环并偶联串联还原与次序羟化反应  

Deciphering Carbamoylpolyoxamic Acid Biosynthesis Reveals Unusual Acetylation Cycle Associated with Tandem Reduction and Sequential Hydroxylation

作　　者：Jianzhao Qi Dan Wan Hongmin Ma Yuanzhen Liu Rong Gong Xudong Qu Yuhui Sun Zixin Deng 陈文青[2] 

机构地区：[1]不详 [2]武汉大学药学院

出　　处：《科学新闻》2017年第4期171-171,共1页Science News

基　　金：国家自然科学基金委;科技部;湖北省科技厅;武汉市科技局;武汉大学相关基金的大力支持

摘　　要：多氧霉素由可可链霉菌阿苏变种和金产色链霉菌产生，该抗生素结构中含有两个非天然的氨基酸结构单元——氨甲酰多氧草氨酸和聚肟酸。尽管氨甲酰多氧草氨酸结构非常独特，然而其生物合成机理一直悬而未决。Polyoxin, produced by Streptomcyes cacaoi var. asoensis and Streptomyces aureochromogenes, contains two non-proteinogenic amino acids, carbamoylpolyoxamic acid (CPOAA) and polyoximic acid. Although the CPOAA moiety is highly unusual, its biosynthetic logic has remained enigmatic for decades. Here, we address CPOAA biosynthesis by reconstitution of its pathway. We demonstrated that its biosynthesis is initiated by a versatile N-acetyltransferase, PolN, catalyzing L-glutamate (1) to N-acetyl glutamate (2). Remarkably, we verified that PolM, a previously annotated dehydrogenase, catalyzes an unprecedented tandem reduction of acyl-phosphate to aldehyde, and subsequently to alcohol. We also unveiled a distinctive acetylation cycle catalyzed by PolN to synthesize alpha-amino-delta-hydroxyvaleric acid (6). Finally, we report that PolL is capable of converting a rare sequential hydroxylation of alpha-amino-delta-carbamoylhydroxyvaleric acid (7) to CPOAA. PolL represents an intriguing family of Fe(II)-dependent alpha-ketoglutarate dioxygenase with a cupin fold. These data illustrate several novel enzymatic reactions, and also set a foundation for rational pathway engineering for polyoxin production.

关 键 词：氨基酸 生物合成 反应 还原 串联 解码 结构单元 序 

分 类 号：Q517[生物学—生物化学]