Choirunnisa Atina Rizkiya, Arima Kuga, Abe Yo, Kagaya Noritaka, Kudo Kei, Suenaga Hikaru, Hashimoto Junko, Fujie Manabu, Satoh Noriyuki, Shin-Ya Kazuo, Matsuda Kenichi, Wakimoto Toshiyuki
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Technology Research Association for Next Generation Natural Products Chemistry, Tokyo 135-0064, Japan.
Beilstein J Org Chem. 2022 Aug 10;18:1017-1025. doi: 10.3762/bjoc.18.102. eCollection 2022.
Only a few azoxy natural products have been identified despite their intriguing biological activities. Azodyrecins D-G, four new analogs of aliphatic azoxides, were identified from two species by a reactivity-based screening that targets azoxy bonds. A biological activity evaluation demonstrated that the double bond in the alkyl side chain is important for the cytotoxicity of azodyrecins. An in vitro assay elucidated the tailoring step of azodyrecin biosynthesis, which is mediated by the -adenosylmethionine (SAM)-dependent methyltransferase Ady1. This study paves the way for the targeted isolation of aliphatic azoxy natural products through a genome-mining approach and further investigations of their biosynthetic mechanisms.
尽管偶氮氧基天然产物具有引人入胜的生物活性，但目前仅鉴定出少数几种。通过基于反应性的筛选方法，从两个物种中鉴定出了偶氮瑞菌素D - G，这是四种新的脂肪族氮氧化物类似物，该筛选方法以偶氮氧基键为目标。生物活性评估表明，烷基侧链中的双键对偶氮瑞菌素的细胞毒性很重要。体外试验阐明了偶氮瑞菌素生物合成的修饰步骤，该步骤由依赖于S -腺苷甲硫氨酸（SAM）的甲基转移酶Ady1介导。这项研究为通过基因组挖掘方法靶向分离脂肪族偶氮氧基天然产物及其生物合成机制的进一步研究铺平了道路。
