Gao Jikai, Wang Wenjing, Yin Ziyang, Ai Jiaying, Lu Fuping, Qin Hui-Min, Mao Shuhong
Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; National Engineering Laboratory for Industrial Enzymes, Tianjin 300457, PR China.
Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; National Engineering Laboratory for Industrial Enzymes, Tianjin 300457, PR China.
Int J Biol Macromol. 2025 Sep;322(Pt 1):146548. doi: 10.1016/j.ijbiomac.2025.146548. Epub 2025 Aug 7.
Unspecific peroxygenases (UPOs) are promising biocatalysts capable of catalysing selective oxygenation of organic substrates using hydrogen peroxide (HO) as the sole oxidant under mild conditions. Sharing a broad substrate range with cytochrome P450 monooxygenases, UPOs function without costly cofactors or auxiliary proteins, making them attractive for industrial biocatalysis. However, limited heterologous expression and poor HO tolerance restrict their broader application. Recent advances in host selection and signal peptide optimisation have significantly improved UPOs production. Simultaneously, various in situ HO generation systems-particularly photobiocatalytic strategies-have enhanced reaction efficiency by stabilising peroxide concentrations. Additionally, efforts to engineer P450s into peroxygenase-like enzymes aim to overcome the limitations of P450s in industrial applications and enhance their utility in organic synthesis. This review systematically summarizes the development of UPOs over the past decade, including technical bottlenecks and future application prospects. The review focuses on heterologous expression, in situ generation of HO, and the modification of P450s to boost peroxygenase activity, providing new ideas for addressing these challenges. In the future, UPOs and P450-derived peroxygenases are anticipated to play an increasingly significant role in green chemistry and organic synthesis.
非特异性过氧酶（UPOs）是一种很有前景的生物催化剂，能够在温和条件下以过氧化氢（HO）作为唯一氧化剂催化有机底物的选择性氧化反应。UPOs与细胞色素P450单加氧酶具有广泛的底物范围，其功能无需昂贵的辅因子或辅助蛋白，这使其在工业生物催化中具有吸引力。然而，有限的异源表达和较差的HO耐受性限制了它们的更广泛应用。宿主选择和信号肽优化方面的最新进展显著提高了UPOs的产量。同时，各种原位HO生成系统——特别是光生物催化策略——通过稳定过氧化物浓度提高了反应效率。此外，将P450s改造为类过氧酶的努力旨在克服P450s在工业应用中的局限性，并提高它们在有机合成中的效用。本综述系统总结了过去十年UPOs的发展，包括技术瓶颈和未来应用前景。综述重点关注异源表达、HO的原位生成以及P450s的修饰以提高过氧酶活性，为应对这些挑战提供新思路。未来，UPOs和P450衍生的过氧酶有望在绿色化学和有机合成中发挥越来越重要的作用。
