{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T22:39:58Z","timestamp":1775860798671,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T00:00:00Z","timestamp":1593216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Polyketide synthases (PKSs) are enzymes that generate diverse molecules of great pharmaceutical importance, including a range of clinically used antimicrobials and antitumor agents. Many polyketides are synthesized by cis-AT modular PKSs, which are organized in assembly lines, in which multiple enzymes line up in a specific order. This order is defined by specific protein\u2013protein interactions (PPIs). The unique modular structure and catalyzing mechanism of these assembly lines makes their products predictable and also spurred combinatorial biosynthesis studies to produce novel polyketides using synthetic biology. However, predicting the interactions of PKSs, and thereby inferring the order of their assembly line, is still challenging, especially for cases in which this order is not reflected by the ordering of the PKS-encoding genes in the genome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we introduce PKSpop, which uses a coevolution-based PPI algorithm to infer protein order in PKS assembly lines. Our method accurately predicts protein orders (93% accuracy). Additionally, we identify new residue pairs that are key in determining interaction specificity, and show that coevolution of N- and C-terminal docking domains of PKSs is significantly more predictive for PPIs than coevolution between ketosynthase and acyl carrier protein domains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The code is available on http:\/\/www.bif.wur.nl\/ (under \u2018Software\u2019).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa595","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T15:13:32Z","timestamp":1592579612000},"page":"4846-4853","source":"Crossref","is-referenced-by-count":12,"title":["Coevolution-based prediction of protein\u2013protein interactions in polyketide biosynthetic assembly lines"],"prefix":"10.1093","volume":"36","author":[{"given":"Yan","family":"Wang","sequence":"first","affiliation":[{"name":"Bioinformatics Group"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3840-3273","authenticated-orcid":false,"given":"Miguel","family":"Correa Marrero","sequence":"additional","affiliation":[{"name":"Bioinformatics Group"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2191-2821","authenticated-orcid":false,"given":"Marnix H","family":"Medema","sequence":"additional","affiliation":[{"name":"Bioinformatics Group"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8872-5123","authenticated-orcid":false,"given":"Aalt D J","family":"van Dijk","sequence":"additional","affiliation":[{"name":"Bioinformatics Group"},{"name":"Department of Plant Sciences Biometris, Wageningen University & Research , 6708 PB Wageningen, The Netherlands"}]}],"member":"286","published-online":{"date-parts":[[2020,6,27]]},"reference":[{"key":"2023062408070704200_btaa595-B1","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1110\/ps.073011407","article-title":"Solution structure and proposed domain-domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase","volume":"16","author":"Alekseyev","year":"2007","journal-title":"Protein Sci"},{"key":"2023062408070704200_btaa595-B2","doi-asserted-by":"crossref","first-page":"W36","DOI":"10.1093\/nar\/gkx319","article-title":"antiSMASH 4.0-improvements in chemistry prediction and gene cluster boundary identification","volume":"45","author":"Blin","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2023062408070704200_btaa595-B3","doi-asserted-by":"crossref","first-page":"D555","DOI":"10.1093\/nar\/gkw960","article-title":"The antiSMASH database, a comprehensive database of microbial secondary metabolite biosynthetic gene clusters","volume":"45","author":"Blin","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2023062408070704200_btaa595-B4","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S1074-5521(03)00156-X","article-title":"The structure of docking domains in modular polyketide synthases","volume":"10","author":"Broadhurst","year":"2003","journal-title":"Chem. 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