Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Accelerated enzyme evolution for targeted C–H oxidation in cyclic amines

Chemical reagents readily oxidize alkyl amines at sites adjacent to nitrogen. Achieving selective oxidation at specified non-adjacent sites is much more challenging. A computation-guided process is introduced that enables rapid optimization of enzymes for site-selective hydroxylation of a variety of cyclic amines.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Docking-guided mutagenesis.


  1. Taylor, R. D., MacCoss, M. & Lawson, A. D. G. Rings in drugs. J. Med. Chem. 57, 5845–5459 (2014). A review article highlighting the importance of nitrogen heterocycles in active pharmaceutical ingredients.

    Article  CAS  Google Scholar 

  2. Hartwig, J. F. & Larsen, M. A. Undirected, homogeneous C–H bond functionalization: challenges and opportunities. ACS Cent. Sci. 2, 281–292 (2016). A review article on chemical reagents for C–H bond activation.

    Article  CAS  Google Scholar 

  3. Chakrabarty, S., Wang, Y., Perkins, J. C. & Narayan, A. R. H. Scalable biocatalytic C–H oxyfunctionalization reactions. Chem. Soc. Rev. 49, 8137–8155 (2020). A review article on the scope of P450-catalysed reactions in synthesis.

    Article  CAS  Google Scholar 

  4. Whitehouse, C. J. C., Bell, S. G. & Wong, L.-L. P450BM3 (CYP102A1): connecting the dots. Chem. Soc. Rev. 41, 1218–1260 (2012). A review on P450BM3 engineering.

    Article  CAS  Google Scholar 

  5. Urlacher, V. B. & Girhard, M. Cytochrome P450 monooxygenases in biotechnology and synthetic biology. Trends Biotechnol. 37, 882–897 (2019). A perspective article on the applications of C–H activation in biotechnology.

    Article  CAS  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Zhang, Y. et al. C–H bonds in cyclic amines by iterative docking-guided mutagenesis of P450BM3 (CYP102A1). Nat. Synth. (2022).

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Accelerated enzyme evolution for targeted C–H oxidation in cyclic amines. Nat. Synth (2022).

Download citation

  • Published:

  • DOI:


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing