Grogan Gideon
Department of Chemistry, University of York, Heslington, York YO10 5DD, United Kingdom.
JACS Au. 2021 Jul 26;1(9):1312-1329. doi: 10.1021/jacsau.1c00251. eCollection 2021 Sep 27.
The selective oxygenation of nonactivated carbon atoms is an ongoing synthetic challenge, and biocatalysts, particularly hemoprotein oxygenases, continue to be investigated for their potential, given both their sustainable chemistry credentials and also their superior selectivity. However, issues of stability, activity, and complex reaction requirements often render these biocatalytic oxygenations problematic with respect to scalable industrial processes. A continuing focus on Cytochromes P450 (P450s), which require a reduced nicotinamide cofactor and redox protein partners for electron transport, has now led to better catalysts and processes with a greater understanding of process requirements and limitations for both in vitro and whole-cell systems. However, the discovery and development of unspecific peroxygenases (UPOs) has also recently provided valuable complementary technology to P450-catalyzed reactions. UPOs need only hydrogen peroxide to effect oxygenations but are hampered by their sensitivity to peroxide and also by limited selectivity. In this Perspective, we survey recent developments in the engineering of proteins, cells, and processes for oxygenations by these two groups of hemoproteins and evaluate their potential and relative merits for scalable reactions.
未活化碳原子的选择性氧化是一个持续存在的合成挑战，鉴于生物催化剂，尤其是血红蛋白加氧酶具有可持续化学特性及其卓越的选择性，它们的潜力仍在持续研究中。然而，稳定性、活性和复杂的反应要求等问题，常常使这些生物催化氧化反应在可扩展的工业过程中存在问题。对细胞色素P450（P450s）的持续关注，这类酶需要还原型烟酰胺辅因子和氧化还原蛋白伴侣进行电子传递，如今随着对体外和全细胞系统过程要求及局限性的更深入了解，已带来了更好的催化剂和工艺。然而，非特异性过氧化物酶（UPOs）的发现与开发最近也为P450催化反应提供了有价值的互补技术。UPOs仅需过氧化氢即可实现氧化反应，但它们对过氧化物敏感且选择性有限，这限制了其应用。在这篇展望文章中，我们综述了这两类血红蛋白在蛋白质、细胞及氧化反应工艺工程方面的最新进展，并评估了它们在可扩展反应中的潜力及相对优势。
