Journal
NATURE CATALYSIS
Volume 6, Issue 1, Pages 89-99Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41929-022-00889-x
Keywords
-
Categories
Ask authors/readers for more resources
The activation of carboxylic acids to thioesters, especially Coenzyme A-based ones, is important but challenging. A generic thioester recycling enzyme, CARsr-A, was developed to catalyze the conversion of carboxylic acids to thioesters. This recycling system can regenerate thioesters for various acyl-S-Coenzyme A-dependent enzymes and enable the formation of diverse amides and non-native acylation reactions.
The activation of carboxylic acids to thioesters plays an important role in biology. However, biochemical studies and biotechnological applications are hampered by a general lack of access to thioesters, especially those based on Coenzyme A (CoA-SH). Here we show a generic thioester recycling enzyme by exploiting the promiscuous activity of a carboxylic acid reductase (CARsr). The adenylation domain of CARsr (CARsr-A) catalyses the conversion of a wide range of carboxylic acids to acyl-S-Coenzyme A and other thioesters in good yields. CARsr-A was used in situ as part of a recycling system to regenerate thioesters for acyl-S-Coenzyme A-dependent enzymes in one-pot reactions. This concept of thioester recycling is demonstrated with a range of acyltransferases that allow the formation of diverse amides and the non-native acylation of lysine side chains in a histone-derived peptide using the epigenetic writer, lysine acetyltransferase HATp300. Overall, these results establish a generic platform for thioester formation towards amide formation and beyond.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available