YcaO explained
YcaO is a protein found in bacteria which is involved in the synthesis of thiazole/oxazole modified microcin antibiotics, such as bottromycin. YcaO performs ATP dependent cyclodehydration to form the oxazole and thiazole moieties of the microcin.[1] [2] [3]
The YcaO name origin is from a gene naming rubric that was established from the bacterium Escherichia coli. If a gene has an unknown function, it was given a four-letter name starting with the letter Y and the next three letters are given based on the genomic location. [4]
Methyl coenzyme M reductase (MCR) or Coenzyme-B sulfoethylthiotransferase is a protein known in thioamidation (a posttranslational modification). A Ycao enzyme dependent on ATP is needed for MCR thioamidation as well as a sulfide source. YcaO enzymes are needed to catalyze the ATP-dependent backbone cyclodehydration of polar amino acids such as Cysteine, Serine, and Threonine to the correct thiazoline and (methyl) oxazoline Heterocycle.[5] The side chains of these amino acids can act as Nucleophiles. The Thiol group in cysteine and the hydroxyl group of serine and threonine are strong nucleophiles.
Notes and References
- Dunbar KL, Melby JO, Mitchell DA . YcaO domains use ATP to activate amide backbones during peptide cyclodehydrations . Nature Chemical Biology . 8 . 6 . 569–575 . April 2012 . 22522320 . 3428213 . 10.1038/nchembio.944 .
- Dunbar KL, Chekan JR, Cox CL, Burkhart BJ, Nair SK, Mitchell DA . Discovery of a new ATP-binding motif involved in peptidic azoline biosynthesis . Nature Chemical Biology . 10 . 10 . 823–829 . October 2014 . 25129028 . 4167974 . 10.1038/nchembio.1608 .
- Koehnke J, Mann G, Bent AF, Ludewig H, Shirran S, Botting C, Lebl T, Houssen W, Jaspars M, Naismith JH . 6 . Structural analysis of leader peptide binding enables leader-free cyanobactin processing . Nature Chemical Biology . 11 . 8 . 558–563 . August 2015 . 26098679 . 4512242 . 10.1038/nchembio.1841 .
- Burkhart BJ, Schwalen CJ, Mann G, Naismith JH, Mitchell DA . YcaO-Dependent Posttranslational Amide Activation: Biosynthesis, Structure, and Function . Chemical Reviews . 117 . 8 . 5389–5456 . April 2017 . 28256131 . 5406272 . 10.1021/acs.chemrev.6b00623 .
- Mahanta N, Liu A, Dong S, Nair SK, Mitchell DA . Enzymatic reconstitution of ribosomal peptide backbone thioamidation . Proceedings of the National Academy of Sciences of the United States of America . 115 . 12 . 3030–3035 . March 2018 . 29507203 . 10.1073/pnas.1722324115 . free . 5866606 .