{"doi":"10.1111/mmi.12088","title":"Acetoacetyl‐<scp>CoA</scp> synthetase activity is controlled by a protein acetyltransferase with unique domain organization in <i>Streptomyces lividans</i>","abstract":"<jats:title>Summary</jats:title><jats:p><jats:styled-content style=\"fixed-case\">GCN</jats:styled-content>5‐type <jats:italic><jats:styled-content style=\"fixed-case\">N</jats:styled-content></jats:italic>‐acetyltransferases (<jats:styled-content style=\"fixed-case\">GNATs</jats:styled-content>) are enzymes that catalyse the transfer of the acetyl group from acetyl‐<jats:styled-content style=\"fixed-case\">CoA</jats:styled-content> to a primary amine. <jats:styled-content style=\"fixed-case\">GNATs</jats:styled-content> are conserved in all domains of life. Some members of this family of enzymes acetylate the side‐chain of specific lysine residues in proteins of diverse function. In bacteria, <jats:styled-content style=\"fixed-case\">GNAT</jats:styled-content>‐catalysed protein acetylation regulates carbon metabolism, <jats:styled-content style=\"fixed-case\">RNA</jats:styled-content> metabolism and transcriptional regulation. Metabolic regulation in <jats:italic><jats:styled-content style=\"fixed-case\">S</jats:styled-content>treptomyces</jats:italic> species is of interest due to the role of these organisms in natural product synthesis. Here we identify <jats:styled-content style=\"fixed-case\"><jats:italic>Sl</jats:italic>PatA</jats:styled-content>, a <jats:styled-content style=\"fixed-case\">GNAT</jats:styled-content> in <jats:italic><jats:styled-content style=\"fixed-case\">S</jats:styled-content>treptomyces lividans</jats:italic> with unique domain organization, and a new acetylation target, namely acetoacetyl‐<jats:styled-content style=\"fixed-case\">CoA</jats:styled-content> synthetase (<jats:styled-content style=\"fixed-case\"><jats:italic>Sl</jats:italic>AacS</jats:styled-content>). The latter has homologues in all domains of life. <jats:italic>In vitro</jats:italic> and <jats:italic>in vivo</jats:italic> evidence show that <jats:styled-content style=\"fixed-case\"><jats:italic>Sl</jats:italic>AacS</jats:styled-content> is a bona fide acetoacetyl‐<jats:styled-content style=\"fixed-case\">CoA</jats:styled-content> synthetase. <jats:styled-content style=\"fixed-case\"><jats:italic>Sl</jats:italic>PatA</jats:styled-content> acetylates <jats:styled-content style=\"fixed-case\"><jats:italic>Sl</jats:italic>AacS</jats:styled-content> more efficiently than it does acetyl‐<jats:styled-content style=\"fixed-case\">CoA</jats:styled-content> synthetase, an enzyme known to be under acetylation control. <jats:styled-content style=\"fixed-case\"><jats:italic>Sl</jats:italic>PatA</jats:styled-content> acetylates <jats:styled-content style=\"fixed-case\"><jats:italic>Sl</jats:italic>AacS</jats:styled-content> at the active‐site residue <jats:styled-content style=\"fixed-case\">Lys</jats:styled-content>617 and acetylation inactivates <jats:styled-content style=\"fixed-case\"><jats:italic>Sl</jats:italic>AacS</jats:styled-content>. Acetylated <jats:styled-content style=\"fixed-case\"><jats:italic>Sl</jats:italic>AacS</jats:styled-content> was deacetylated by a sirtuin‐type protein deacetylase. <jats:styled-content style=\"fixed-case\"><jats:italic>Sl</jats:italic>AacS</jats:styled-content> acetylation/deacetylation may represent a conserved mechanism for regulation of acetoacetyl‐<jats:styled-content style=\"fixed-case\">CoA</jats:styled-content> synthetase activity in all domains of life.</jats:p>","journal":"Molecular Microbiology","year":2013,"id":14574,"datarank":1.7926615002247919,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"self_citation_contribution":0.5897738449086489,"citation_network_contribution":1.202887655316143,"self_endowment_contribution":0.5897738449086489,"citer_contribution":1.202887655316143,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"citer_count":39,"citers_with_citation_signal":34,"citers_with_endowment":34,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":114512,"name":"Jorge C. 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