Nicotine oxidoreductase (NicA2), a member of the flavin-containing amine oxidase family, is of medical relevance as it shows potential as a therapeutic to aid cessation of smoking due to its ability to oxidize nicotine into a non-psychoactive metabolite. However, the use of NicA2 in this capacity is stymied by its dismal O₂-dependent activity. Unlike other enzymes in the amine oxidase family, NicA2 reacts very slowly with O₂, severely limiting its nicotine-degrading activity. Instead of using O₂ as an oxidant, we discovered that NicA2 donates electrons to a cytochrome c, which means that NicA2 is actually a dehydrogenase. This is surprising, as enzymes of the flavin-containing amine oxidase family were invariably thought to use O₂ as an electron acceptor. Our findings establish new perspectives for engineering this potentially useful therapeutic and prompt a reconsideration of the term ‘oxidase’ in referring to members of the flavin-containing amine ‘oxidase’ family.

尼古丁氧化还原酶 (NicA2) 是含黄素胺氧化酶家族的一员，具有医学相关性，因为它具有将尼古丁氧化成非精神活性代谢物的能力，因此显示出作为辅助戒烟治疗剂的潜力。然而，NicA2 以这种能力使用受到其令人沮丧的 O ₂依赖性活动的阻碍。与胺氧化酶家族中的其他酶不同，NicA2 与 O ₂的反应非常缓慢，严重限制了其尼古丁降解活性。我们没有使用 O ₂作为氧化剂，而是发现 NicA2 向细胞色素c提供电子，这意味着 NicA2 实际上是一种脱氢酶。这是令人惊讶的，因为含黄素的胺氧化酶家族的酶总是被认为使用 O₂作为电子受体。我们的研究结果为设计这种潜在有用的治疗药物建立了新的视角，并促使人们重新考虑术语“氧化酶”来指代含黄素的胺“氧化酶”家族的成员。