title: YcaO-Dependent Posttranslational Amide Activation: Biosynthesis, Structure, and Function.
abstract: With advances in sequencing technology, uncharacterized proteins and domains of unknown function (DUFs) are rapidly accumulating in sequence databases and offer an opportunity to discover new protein chemistry and reaction mechanisms. The focus of this review, the formerly enigmatic YcaO superfamily (DUF181), has been found to catalyze a unique phosphorylation of a ribosomal peptide backbone amide upon attack by different nucleophiles. Established nucleophiles are the side chains of Cys, Ser, and Thr which gives rise to azoline/azole biosynthesis in ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products. However, much remains unknown about the potential for YcaO proteins to collaborate with other nucleophiles. Recent work suggests potential in forming thioamides, macroamidines, and possibly additional post-translational modifications. This review covers all knowledge through mid-2016 regarding the biosynthetic gene clusters (BGCs), natural products, functions, mechanisms, and applications of YcaO proteins and outlines likely future research directions for this protein superfamily.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Burkhart
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schwalen
authors.affiliation: Biomedical Science Research Complex, University of St Andrews , BSRC North Haugh, St Andrews KY16 9ST, United Kingdom.
authors.forename: Greg
authors.initials: G
authors.lastname: Mann
authors.affiliation: Biomedical Science Research Complex, University of St Andrews , BSRC North Haugh, St Andrews KY16 9ST, United Kingdom.|State Key Laboratory of Biotherapy, Sichuan University , Sichuan, China.
authors.forename: James H
authors.identifier: http://orcid.org/0000-0001-6744-5061
authors.initials: JH
authors.lastname: Naismith
authors.forename: Douglas A
authors.identifier: http://orcid.org/0000-0002-9564-0953
authors.initials: DA
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D001393:Azoles / Q000032:analysis; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013329:Structure-Activity Relationship
chemical_list: D001393:Azoles; D010455:Peptides