Document Type


Publication Date



Daptomycin (DAP) is a calcium (Ca2+)‐dependent FDA‐approved antibiotic drug for the treatment of Gram‐positive infections. It possesses a complex pharmacophore hampering derivatization and/or synthesis of analogs. In order to mimic the Ca2+‐binding effect we uses a chemoenzymatic approach to modify the tryptophan (Trp) residue of DAP and synthesize kinetically characterized and structurally elucidated regiospecific Trp‐modified DAP analogs. We demonstrated that the modified DAPs are several‐folds active than the parent molecule against antibiotic‐susceptible and antibiotic‐resistant Gram‐positive bacteria. Strikingly and in contrast to the parent molecule, the DAP derivatives do not rely on calcium or any additional elements for activity.


This is the accepted version of the following article:

Mupparapu N, Lin YC, Kim TH, Elshahawi SI. Regiospecific synthesis of calcium-independent daptomycin antibiotics using a chemoenzymatic method. Chemistry. 2020;10.1002/chem.202005100.

which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.





To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.