Enzymes catalyze the formation of intermediates and products in a mild and "greener" manner under physiologial temperature and pH. Thus, biocatalysis has gained much interest in recent years to faciltate difficult to achieve chemical reactions. We have developed a chemoenzymatic platform that is capable of modifying drugs with aromatic moieties. Aromatic prenyltransferases that have been overproduced and purified as well as alkyl and aryl pyrophosphates were used to derivatize aromatic drugs in our lab. We have applied our chemoenzymatic platform to modify daptomycin, a calcium-dependent FDA-approved antibiotic drug used for the treatment of bacteremia and skin structure infections. The enzymatically synthesized and regiospecific analogs were purified and their structures were elucidated using 1- and 2D NMR and HR-MS and found to be active against daptomycin-resistant bacteria. Most importantly, the analogs were found to be active in the absence of calcium in contrast to the parent daptomycin.

Enzymatic synthesis of calcium-independent superior daptomycin analogs

ACS Spring Meeting 2021

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