Bacterial Avenalumic Acid Biosynthesis Includes Substitution of an Aromatic Amino Group for Hydride by Nitrous Acid Dependent Diazotization
Bacterial Avenalumic Acid Biosynthesis Includes Substitution of an Aromatic Amino Group for Hydride by Nitrous Acid Dependent Diazotization
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DOI：
10.1002/anie.202211728
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发表时间：
2022-10-07
影响因子：
16.6
通讯作者：
Ohnishi, Yasuo
中科院分区：
文献类型：
--
作者：
Kawai, Seiji;Hagihara, Ryota;Ohnishi, Yasuo
重氮基是一种重要的官能团，具有很高的反应活性，可以赋予天然产物生物活性。最近的研究表明，重氮基是利用放线菌次级代谢产物中的亚硝酸由氨基合成的。然而，基因组数据库分析表明，对于未知的生物合成途径，仍然存在许多重氮基团生物合成酶。在此，我们在链霉菌中发现了一个燕麦酸类生物合成基因簇。RI-77通过基因组挖掘参与重氮基团的形成。通过异源表达，发现该基因簇通过3-氨基铝酸(3-AAA)直接生物合成AVA。体外酶分析表明，AvaA6和AvaA7分别催化3-AAA的亚硝酸重氮化和重氮基取代氢化物合成AVA。这项研究揭示了一种前所未有的通过重氮化去除氨基的途径。
The diazo group is an important functional group that can confer biological activity to natural products owing to its high reactivity. Recent studies have revealed that diazo groups are synthesized from amino groups using nitrous acid in secondary metabolites of actinomycetes. However, genome database analysis indicated that there are still many diazo group-biosynthesizing enzymes for unknown biosynthetic pathways. Here, we discovered an avenalumic acid biosynthesis gene cluster in Streptomyces sp. RI-77 by genome mining of enzymes involved in diazo group formation. Through heterologous expression, the gene cluster was revealed to direct avenalumic acid (AVA) biosynthesis via 3-aminoavenalumic acid (3-AAA). In vitro enzyme assays showed that AvaA6 and AvaA7 catalyzed the diazotization of 3-AAA using nitrous acid and substitution of the diazo group for hydride to synthesize AVA, respectively. This study revealed an unprecedented pathway for amino group removal via diazotization.