{"id":"https://openalex.org/W2004887402","doi":"https://doi.org/10.1021/ja038166y","title":"The Post-Polyketide Synthase Modification Steps in the Biosynthesis of the Antitumor Agent Ansamitocin by Actinosynnema pretiosum","display_name":"The Post-Polyketide Synthase Modification Steps in the Biosynthesis of the Antitumor Agent Ansamitocin by Actinosynnema pretiosum","publication_year":2003,"publication_date":"2003-11-01","ids":{"openalex":"https://openalex.org/W2004887402","doi":"https://doi.org/10.1021/ja038166y","mag":"2004887402","pmid":"https://pubmed.ncbi.nlm.nih.gov/14624546"},"language":"en","primary_location":{"id":"doi:10.1021/ja038166y","doi":"https://doi.org/10.1021/ja038166y","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ja038166y","pdf_url":null,"source":{"id":"https://openalex.org/S111155417","display_name":"Journal of the American Chemical Society","issn_l":"0002-7863","issn":["0002-7863","1520-5126","1943-2984"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the American Chemical Society","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5026173866","display_name":"Peter Spiteller","orcid":"https://orcid.org/0000-0003-2916-4319","observed_orcids":["https://orcid.org/0000-0003-2916-4319"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Peter Spiteller","raw_affiliation_strings":["Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005490679","display_name":"Linquan Bai","orcid":"https://orcid.org/0000-0002-3269-9747","observed_orcids":["https://orcid.org/0000-0002-3269-9747"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Linquan Bai","raw_affiliation_strings":["Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045074373","display_name":"Guangdong Shang","orcid":"https://orcid.org/0000-0001-6142-3785","observed_orcids":["https://orcid.org/0000-0001-6142-3785"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Guangdong Shang","raw_affiliation_strings":["Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102808725","display_name":"Brian J. Carroll","orcid":"https://orcid.org/0000-0001-9613-4641","observed_orcids":["https://orcid.org/0000-0001-9613-4641"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Brian J. Carroll","raw_affiliation_strings":["Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112446571","display_name":"Tin\u2010Wein Yu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Tin-Wein Yu","raw_affiliation_strings":["Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5027410094","display_name":"Heinz G. Floss","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Heinz G. Floss","raw_affiliation_strings":["Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Box 351700, University of Washington, Seattle, Washington 98195-1700","institution_ids":["https://openalex.org/I201448701"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I201448701"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":2.1433,"has_fulltext":false,"cited_by_count":79,"citation_normalized_percentile":{"value":0.85249764,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"125","issue":"47","first_page":"14236","last_page":"14237"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10252","display_name":"Microbial Natural Products and Biosynthesis","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10252","display_name":"Microbial Natural Products and Biosynthesis","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12673","display_name":"Microbial Metabolism and Applications","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1305","display_name":"Biotechnology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12530","display_name":"Bioactive Natural Diterpenoids Research","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/ansamitocins","display_name":"ansamitocins","score":0.9729999899864197},{"id":"https://openalex.org/keywords/actinosynnema-pretiosum","display_name":"Actinosynnema pretiosum","score":0.9639999866485596},{"id":"https://openalex.org/keywords/biosynthetic-gene-clusters","display_name":"biosynthetic gene clusters","score":0.7979999780654907},{"id":"https://openalex.org/keywords/halogenase","display_name":"halogenase","score":0.9380000233650208},{"id":"https://openalex.org/keywords/epoxidase","display_name":"epoxidase","score":0.9950000047683716},{"id":"https://openalex.org/keywords/n-methyltransferase","display_name":"N-methyltransferase","score":1.0},{"id":"https://openalex.org/keywords/gene-inactivation","display_name":"gene inactivation","score":0.7049999833106995},{"id":"https://openalex.org/keywords/anticancer-natural-products","display_name":"anticancer natural products","score":0.7360000014305115},{"id":"https://openalex.org/keywords/substrate-specificity","display_name":"substrate specificity","score":0.753000020980835}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.818541407585144},{"id":"https://openalex.org/C2775970874","wikidata":"https://www.wikidata.org/wiki/Q2609152","display_name":"Acyltransferase","level":3,"score":0.7573270797729492},{"id":"https://openalex.org/C2777763344","wikidata":"https://www.wikidata.org/wiki/Q4369963","display_name":"Polyketide synthase","level":5,"score":0.7195426225662231},{"id":"https://openalex.org/C36857842","wikidata":"https://www.wikidata.org/wiki/Q1501261","display_name":"Gene cluster","level":3,"score":0.6648364067077637},{"id":"https://openalex.org/C553450214","wikidata":"https://www.wikidata.org/wiki/Q851162","display_name":"Biosynthesis","level":3,"score":0.6468117237091064},{"id":"https://openalex.org/C2778635478","wikidata":"https://www.wikidata.org/wiki/Q516751","display_name":"Polyketide","level":4,"score":0.639481246471405},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.5949319005012512},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.5866019129753113},{"id":"https://openalex.org/C91965660","wikidata":"https://www.wikidata.org/wiki/Q415875","display_name":"Methyltransferase","level":4,"score":0.5329452753067017},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.5233699083328247},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.5186354517936707},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.490220844745636},{"id":"https://openalex.org/C33288867","wikidata":"https://www.wikidata.org/wiki/Q518328","display_name":"Methylation","level":3,"score":0.08188030123710632}],"mesh":[{"descriptor_ui":"D000192","descriptor_name":"Actinomycetales","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D000192","descriptor_name":"Actinomycetales","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D000192","descriptor_name":"Actinomycetales","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000903","descriptor_name":"Antibiotics, Antineoplastic","qualifier_ui":"Q000096","qualifier_name":"biosynthesis","is_major_topic":true},{"descriptor_ui":"D008453","descriptor_name":"Maytansine","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":true},{"descriptor_ui":"D008453","descriptor_name":"Maytansine","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D009097","descriptor_name":"Multienzyme Complexes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/ja038166y","doi":"https://doi.org/10.1021/ja038166y","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ja038166y","pdf_url":null,"source":{"id":"https://openalex.org/S111155417","display_name":"Journal of the American Chemical Society","issn_l":"0002-7863","issn":["0002-7863","1520-5126","1943-2984"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the American Chemical Society","raw_type":"journal-article"},{"id":"pmid:14624546","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/14624546","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the American Chemical Society","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G3286679413","display_name":"Biosynthesis of Maytansinoids and Analogs","funder_award_id":"R01CA076461","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G4367561413","display_name":null,"funder_award_id":"CA 76461","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":4,"referenced_works":["https://openalex.org/W1974049496","https://openalex.org/W1980711178","https://openalex.org/W2017818060","https://openalex.org/W2165166213"],"related_works":["https://openalex.org/W2133731751","https://openalex.org/W2008606425","https://openalex.org/W2753731740","https://openalex.org/W2033666439","https://openalex.org/W2046357515","https://openalex.org/W7130434777","https://openalex.org/W2053821409","https://openalex.org/W2463794011","https://openalex.org/W2085683870","https://openalex.org/W2787053636"],"abstract_inverted_index":{"The":[0],"functions":[1],"of":[2,11,23,61,82],"six":[3,53],"genes":[4],"in":[5,57,69,73],"the":[6,24,52,62],"ansamitocin":[7,58],"biosynthetic":[8],"gene":[9,18],"cluster":[10],"Actinosynnema":[12],"pretiosum":[13],"have":[14,64],"been":[15],"investigated":[16],"by":[17],"inactivation":[19],"and":[20,43,48],"chemical":[21],"analysis":[22],"mutants.":[25],"They":[26],"encode":[27],"a":[28,31,34,37,74,79],"halogenase":[29],"(asm12),":[30],"carbamoyltransferase":[32],"(asm21),":[33],"20-O-methyltransferase":[35],"(asm7),":[36],"3-O-acyltransferase":[38],"(asm19),":[39],"an":[40,44],"epoxidase":[41],"(asm11),":[42],"N-methyltransferase":[45],"(asm10),":[46],"respectively,":[47],"are":[49],"responsible":[50],"for":[51],"post-PKS":[54],"modification":[55],"steps":[56],"formation.":[59],"Several":[60],"enzymes":[63],"relaxed":[65],"substrate":[66],"specificities,":[67],"resulting":[68],"multiple":[70],"parallel":[71],"pathways":[72],"metabolic":[75],"grid,":[76],"albeit":[77],"with":[78],"preferred":[80],"sequence":[81],"reactions":[83],"as":[84],"listed":[85],"above.":[86]},"counts_by_year":[{"year":2026,"cited_by_count":4},{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":2},{"year":2022,"cited_by_count":2},{"year":2021,"cited_by_count":2},{"year":2020,"cited_by_count":6},{"year":2019,"cited_by_count":2},{"year":2018,"cited_by_count":1},{"year":2017,"cited_by_count":4},{"year":2016,"cited_by_count":6},{"year":2015,"cited_by_count":3},{"year":2014,"cited_by_count":4},{"year":2013,"cited_by_count":3},{"year":2012,"cited_by_count":4}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}