Unlocking new chemistries in extant enzymes for synthesizing bioactive molecules

Active Project Grant Awarded Last action

Award ID
R00GM152783
Recipient
Awarding agency
Obligated
$498,000

Award facts

Assistance listing
93.859 Biomedical Research and Research Training
Completion date 38% complete
Place of performance
Durham, NC 27705, USA

Award details come from USAspending.gov.

Description

Abstract
Enzymes, supported by their macromolecular structure, can catalyze chemical transformations with exquisite control, delivering products with high selectivity. The mechanisms that enzymes can support, however, are limited, making chemical technologies often the preferred method for synthesis, regardless of cost, toxicity, and environmental burden. Herein are two proposals to expand the activity of enzymes beyond their natural function for synthesizing medicinally important functional groups. Specifically, heme enzymes and methionine sulfoxide reductases are tasked for the first time with performing aminations and oxidations, respectively, toward synthesizing chiral trifluoroethylamines, sulfoxides, and sulfoximines, motifs known to bestow function and drug- like properties to therapeutics and clinical candidates. By engineering enzymes to catalyze reactions beyond their natural capabilities, we are boldly pushing the boundaries of biology and chemistry. This innovation has the potential to revolutionize the way we make molecules and introduce new chemical reactions that can be performed in living organisms. Furthermore, these efforts will unlock activities never before seen in biocatalysis, expanding the repertoire of genetically encoded chemical transformations. The success of this proposal will afford high-value molecules and biorenewable catalysts that may lead to the discovery of new medicines and strategies to regulate biology, with the ultimate objective of informing and improving human health.

Transactions

Action Obligated Date
Amendment $249,000
Original award $249,000

Quick answers

Who received award R00GM152783?

R00GM152783 was awarded to Duke University by National Institute of General Medical Sciences (National Institutes of Health) on September 1, 2025.

How much is award R00GM152783 worth?

$498,000 has been obligated on R00GM152783.

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