The growing prevalence of synthetically modified proteins in pharmaceuticals and materials has exposed the need for efficient strategies to enable chemical modifications with high site-selectivity. While genetic engineering can incorporate non-natural amino acids into recombinant proteins, regioselective chemical modification of wild-type proteins remains a challenge. Herein, we use photoredox catalysis to develop a site-selective tyrosine bioconjugation pathway that incorporates bioorthogonal formyl groups, which subsequently allows for the synthesis of structurally defined fluorescent conjugates from native proteins. A water-soluble photocatalyst, lumiflavin, has been shown to induce oxidative coupling between a previously unreported phenoxazine dialdehyde tag and a single tyrosine site, even in the presence of multiple tyrosyl side chains, through the formation of a covalent C–N bond. A variety of native proteins, including those with multiple tyrosines, can successfully undergo both tyrosine-specific and single-site-selective labelling. This technology directly introduces aldehyde moieties onto native proteins, enabling rapid product diversification using an array of well-established bioorthogonal functionalization protocols including the alkyne–azide click reaction.

药物和材料中合成修饰蛋白质的日益流行暴露了对有效策略的需求，以实现具有高位点选择性的化学修饰。虽然基因工程可以将非天然氨基酸整合到重组蛋白中，但野生型蛋白的区域选择性化学修饰仍然是一个挑战。在这里，我们使用光氧化还原催化来开发一种位点选择性酪氨酸生物偶联途径，该途径包含生物正交甲酰基，随后允许从天然蛋白质合成结构定义的荧光偶联物。即使在存在多个酪氨酰侧链的情况下，水溶性光催化剂 Lumiflavin 也已被证明可诱导先前未报道的吩恶嗪二醛标签和单个酪氨酸位点之间的氧化偶联，通过形成共价C-N键。多种天然蛋白质，包括具有多个酪氨酸的蛋白质，可以成功地进行酪氨酸特异性和单位点选择性标记。该技术直接将醛部分引入天然蛋白质，使用一系列成熟的生物正交功能化协议（包括炔烃-叠氮化物点击反应）实现快速产品多样化。