Structural basis for selectivity in a highly reducing type II polyketide synthase

In type II polyketide synthases (PKSs), the ketosynthase–chain length factor (KS–CLF) complex catalyzes polyketide chain elongation with the acyl carrier protein (ACP). Highly reducing type II PKSs, represented by IgaPKS, produce polyene structures instead of the well-known aromatic skeletons. Here,...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Nature chemical biology Ročník 16; číslo 7; s. 776 - 782
Hlavní autoři:	Du, Danyao, Katsuyama, Yohei, Horiuchi, Masanobu, Fushinobu, Shinya, Chen, Aochiu, Davis, Tony D., Burkart, Michael D., Ohnishi, Yasuo
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.07.2020 Nature Publishing Group
Témata:	631/535/1266 631/92/60 631/92/607 Acyl carrier protein Acyl Carrier Protein - chemistry Acyl Carrier Protein - genetics Acyl Carrier Protein - metabolism Antifungal agents Biocatalysis Biochemical Engineering Biochemistry Bioorganic Chemistry Biosynthesis Catalytic Domain Cell Biology Chemistry Chemistry and Materials Science Chemistry/Food Science Cloning, Molecular Condensates Condensation Crosslinking Crystal structure Crystallography, X-Ray E coli Elongation Escherichia coli - enzymology Escherichia coli - genetics Escherichia coli Proteins - chemistry Escherichia coli Proteins - genetics Escherichia coli Proteins - metabolism Fatty Acid Synthases - chemistry Fatty Acid Synthases - genetics Fatty Acid Synthases - metabolism Fatty acids Fatty-acid synthase Gene Expression Genetic Vectors - chemistry Genetic Vectors - metabolism Models, Molecular Molecular interactions Molecular structure Mutagenesis Mutagenesis, Site-Directed Polyketide synthase Polyketide Synthases - chemistry Polyketide Synthases - genetics Polyketide Synthases - metabolism Polyketides - chemistry Polyketides - metabolism Protein Binding Protein Conformation, alpha-Helical Protein Conformation, beta-Strand Protein Interaction Domains and Motifs Protein Multimerization Proteins Recombinant Proteins - chemistry Recombinant Proteins - genetics Recombinant Proteins - metabolism Selectivity Site-directed mutagenesis Streptomyces - enzymology Streptomyces - genetics Substrate Specificity Substrates
ISSN:	1552-4450, 1552-4469, 1552-4469
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Abstract	In type II polyketide synthases (PKSs), the ketosynthase–chain length factor (KS–CLF) complex catalyzes polyketide chain elongation with the acyl carrier protein (ACP). Highly reducing type II PKSs, represented by IgaPKS, produce polyene structures instead of the well-known aromatic skeletons. Here, we report the crystal structures of the Iga11–Iga12 (KS–CLF) heterodimer and the covalently cross-linked Iga10=Iga11–Iga12 (ACP=KS–CLF) tripartite complex. The latter structure revealed the molecular basis of the interaction between Iga10 and Iga11–Iga12, which differs from that between the ACP and KS of Escherichia coli fatty acid synthase. Furthermore, the reaction pocket structure and site-directed mutagenesis revealed that the negative charge of Asp 113 of Iga11 prevents further condensation using a β-ketoacyl product as a substrate, which distinguishes IgaPKS from typical type II PKSs. This work will facilitate the future rational design of PKSs. Structures of the ketosynthase–chain length factor complex from ishigamide biosynthesis, cross-linked to the acyl carrier protein, reveal the molecular interactions between these domains and how the reaction pocket limits rounds of product extension.
AbstractList	In type II polyketide synthases (PKSs), the ketosynthase-chain length factor (KS-CLF) complex catalyzes polyketide chain elongation with the acyl carrier protein (ACP). Highly reducing type II PKSs, represented by IgaPKS, produce polyene structures instead of the well-known aromatic skeletons. Here, we report the crystal structures of the Iga11-Iga12 (KS-CLF) heterodimer and the covalently cross-linked Iga10=Iga11-Iga12 (ACP=KS-CLF) tripartite complex. The latter structure revealed the molecular basis of the interaction between Iga10 and Iga11-Iga12, which differs from that between the ACP and KS of Escherichia coli fatty acid synthase. Furthermore, the reaction pocket structure and site-directed mutagenesis revealed that the negative charge of Asp 113 of Iga11 prevents further condensation using a β-ketoacyl product as a substrate, which distinguishes IgaPKS from typical type II PKSs. This work will facilitate the future rational design of PKSs. In type II polyketide synthases (PKSs), the ketosynthase–chain length factor (KS–CLF) complex catalyzes polyketide chain elongation with the acyl carrier protein (ACP). Highly reducing type II PKSs, represented by IgaPKS, produce polyene structures instead of the well-known aromatic skeletons. Here, we report the crystal structures of the Iga11–Iga12 (KS–CLF) heterodimer and the covalently cross-linked Iga10=Iga11–Iga12 (ACP=KS–CLF) tripartite complex. The latter structure revealed the molecular basis of the interaction between Iga10 and Iga11–Iga12, which differs from that between the ACP and KS of Escherichia coli fatty acid synthase. Furthermore, the reaction pocket structure and site-directed mutagenesis revealed that the negative charge of Asp 113 of Iga11 prevents further condensation using a β-ketoacyl product as a substrate, which distinguishes IgaPKS from typical type II PKSs. This work will facilitate the future rational design of PKSs.Structures of the ketosynthase–chain length factor complex from ishigamide biosynthesis, cross-linked to the acyl carrier protein, reveal the molecular interactions between these domains and how the reaction pocket limits rounds of product extension. In type II polyketide synthases (PKSs), the ketosynthase-chain length factor (KS-CLF) complex catalyzes polyketide chain elongation with the acyl carrier protein (ACP). Highly reducing type II PKSs, represented by IgaPKS, produce polyene structures instead of the well-known aromatic skeletons. Here, we report the crystal structures of the Iga11-Iga12 (KS-CLF) heterodimer and the covalently cross-linked Iga10=Iga11-Iga12 (ACP=KS-CLF) tripartite complex. The latter structure revealed the molecular basis of the interaction between Iga10 and Iga11-Iga12, which differs from that between the ACP and KS of Escherichia coli fatty acid synthase. Furthermore, the reaction pocket structure and site-directed mutagenesis revealed that the negative charge of Asp 113 of Iga11 prevents further condensation using a β-ketoacyl product as a substrate, which distinguishes IgaPKS from typical type II PKSs. This work will facilitate the future rational design of PKSs.In type II polyketide synthases (PKSs), the ketosynthase-chain length factor (KS-CLF) complex catalyzes polyketide chain elongation with the acyl carrier protein (ACP). Highly reducing type II PKSs, represented by IgaPKS, produce polyene structures instead of the well-known aromatic skeletons. Here, we report the crystal structures of the Iga11-Iga12 (KS-CLF) heterodimer and the covalently cross-linked Iga10=Iga11-Iga12 (ACP=KS-CLF) tripartite complex. The latter structure revealed the molecular basis of the interaction between Iga10 and Iga11-Iga12, which differs from that between the ACP and KS of Escherichia coli fatty acid synthase. Furthermore, the reaction pocket structure and site-directed mutagenesis revealed that the negative charge of Asp 113 of Iga11 prevents further condensation using a β-ketoacyl product as a substrate, which distinguishes IgaPKS from typical type II PKSs. This work will facilitate the future rational design of PKSs. In type II polyketide synthases (PKSs), the ketosynthase–chain length factor (KS–CLF) complex catalyzes polyketide chain elongation with the acyl carrier protein (ACP). Highly reducing type II PKSs, represented by IgaPKS, produce polyene structures instead of the well-known aromatic skeletons. Here, we report the crystal structures of the Iga11–Iga12 (KS–CLF) heterodimer and the covalently cross-linked Iga10=Iga11–Iga12 (ACP=KS–CLF) tripartite complex. The latter structure revealed the molecular basis of the interaction between Iga10 and Iga11–Iga12, which differs from that between the ACP and KS of Escherichia coli fatty acid synthase. Furthermore, the reaction pocket structure and site-directed mutagenesis revealed that the negative charge of Asp 113 of Iga11 prevents further condensation using a β-ketoacyl product as a substrate, which distinguishes IgaPKS from typical type II PKSs. This work will facilitate the future rational design of PKSs. Structures of the ketosynthase–chain length factor complex from ishigamide biosynthesis, cross-linked to the acyl carrier protein, reveal the molecular interactions between these domains and how the reaction pocket limits rounds of product extension.
Author	Katsuyama, Yohei Du, Danyao Ohnishi, Yasuo Horiuchi, Masanobu Chen, Aochiu Burkart, Michael D. Davis, Tony D. Fushinobu, Shinya
AuthorAffiliation	1 Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan 3 Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA, USA 2 Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo, Japan
AuthorAffiliation_xml	– name: 2 Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo, Japan – name: 3 Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA, USA – name: 1 Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
Author_xml	– sequence: 1 givenname: Danyao surname: Du fullname: Du, Danyao organization: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo – sequence: 2 givenname: Yohei orcidid: 0000-0003-4905-5320 surname: Katsuyama fullname: Katsuyama, Yohei email: aykatsu@mail.ecc.u-tokyo.ac.jp organization: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Collaborative Research Institute for Innovative Microbiology, The University of Tokyo – sequence: 3 givenname: Masanobu surname: Horiuchi fullname: Horiuchi, Masanobu organization: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo – sequence: 4 givenname: Shinya orcidid: 0000-0003-1346-6435 surname: Fushinobu fullname: Fushinobu, Shinya organization: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Collaborative Research Institute for Innovative Microbiology, The University of Tokyo – sequence: 5 givenname: Aochiu orcidid: 0000-0002-9143-7392 surname: Chen fullname: Chen, Aochiu organization: Department of Chemistry and Biochemistry, University of California, San Diego – sequence: 6 givenname: Tony D. orcidid: 0000-0001-5629-7075 surname: Davis fullname: Davis, Tony D. organization: Department of Chemistry and Biochemistry, University of California, San Diego – sequence: 7 givenname: Michael D. orcidid: 0000-0002-4472-2254 surname: Burkart fullname: Burkart, Michael D. email: mburkart@ucsd.edu organization: Department of Chemistry and Biochemistry, University of California, San Diego – sequence: 8 givenname: Yasuo surname: Ohnishi fullname: Ohnishi, Yasuo organization: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Collaborative Research Institute for Innovative Microbiology, The University of Tokyo
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/32367018$$D View this record in MEDLINE/PubMed
BookMark	eNp9kV1rFDEYhUOp9NMf4I0EvPFmbJLJ194IUlpdKBTRXods5p3d1NlkTTKF-fdmu3XVgr1JAnnOec_LOUWHIQZA6A0lHyhp9UXmVOhZQxhpiGjrcYBOqBCs4VzODvdvQY7Rac73hLRSUn2EjlvWSkWoPkFfv5U0ujImO-CFzT7jPiacYQBX_IMvE_YBW7zyy9Uw4QTd6HxY4jJtAM_neBOH6QcU3wHOUygrm-EcvertkOH1032G7q6vvl9-aW5uP88vP900TkheGqlsBzOrRU-E6hRZEKb5ohO26znjYJ3Q2sq-awVnqtcg7DY9c73lmlkF7Rn6uPPdjIs1dA5CqUuYTfJrmyYTrTf__gS_Msv4YJQQUlFZDd4_GaT4c4RczNpnB8NgA8QxG9bOtGSMEl7Rd8_Q-zimUNczjCuplGSPhi9QtQtFmBCVevt37n3g351UgO4Al2LOCfo9QonZ9m52vZvau9n2bkjVqGca54stPm5X98OLSrZT5jolLCH9Cf1_0S_D9cEj
CitedBy_id	crossref_primary_10_3762_bjoc_20_69 crossref_primary_10_1002_pro_70229 crossref_primary_10_3389_fchem_2025_1582515 crossref_primary_10_1021_jacs_5c05635 crossref_primary_10_1126_science_abi8532 crossref_primary_10_1002_ange_202200879 crossref_primary_10_1002_cbic_202200775 crossref_primary_10_1111_cbdd_13851 crossref_primary_10_3390_ijms24108923 crossref_primary_10_1002_cbic_202000747 crossref_primary_10_1021_jacs_3c10181 crossref_primary_10_1126_science_abq7333 crossref_primary_10_3987_REV_22_986 crossref_primary_10_1038_s41467_023_43731_z crossref_primary_10_1038_s41598_021_95890_y crossref_primary_10_1021_jacs_2c02855 crossref_primary_10_1002_cbic_202100517 crossref_primary_10_1016_j_bmc_2020_115686 crossref_primary_10_1016_j_tetlet_2022_154183 crossref_primary_10_1038_s41467_023_36989_w crossref_primary_10_1002_cbic_202200200 crossref_primary_10_1002_anie_202200879 crossref_primary_10_1016_j_jbc_2022_102480 crossref_primary_10_1016_j_str_2022_05_021 crossref_primary_10_1038_s41467_025_62168_0 crossref_primary_10_3390_agronomy14112747 crossref_primary_10_1038_s41589_023_01277_7 crossref_primary_10_1093_bbb_zbaa023 crossref_primary_10_1039_D1SC07256K crossref_primary_10_3762_bjoc_20_1 crossref_primary_10_1007_s10343_025_01148_2 crossref_primary_10_1107_S2059798322007434 crossref_primary_10_1016_j_jbc_2021_100328 crossref_primary_10_1021_jacs_0c13378
Cites_doi	10.1038/s41589-019-0301-y 10.1039/C8NP00030A 10.1039/C8NP00040A 10.1021/bi992121l 10.1074/jbc.M513199200 10.1021/jacs.8b10776 10.1021/ja5064857 10.1107/S0907444913000061 10.1107/S0907444904023510 10.1107/S0907444994003112 10.1039/B507395M 10.1002/cbic.201402578 10.1146/annurev-biochem-063011-164509 10.1038/nature12810 10.1002/cbic.200800198 10.1039/c2np20062g 10.1039/B512735A 10.1107/S0907444909047337 10.1107/S0907444909042589 10.1002/cbic.201600167 10.1021/jacs.8b04162 10.1038/s41589-018-0026-3 10.1038/nprot.2015.053 10.1107/S0907444909052925 10.1074/jbc.274.10.6031 10.1021/ja052911k 10.1073/pnas.1818686116 10.1107/S0907444910007493 10.1002/anie.201709636 10.1073/pnas.1520042113 10.1111/febs.12785 10.1002/anie.200806121 10.1038/nature04784 10.1016/j.bmcl.2008.01.026 10.1039/a909079g 10.1016/j.bmcl.2009.02.006 10.1038/srep14797 10.1021/ar8002249 10.1038/nsmb808 10.1021/cb6003965
ContentType	Journal Article
Copyright	The Author(s), under exclusive licence to Springer Nature America, Inc. 2020 The Author(s), under exclusive licence to Springer Nature America, Inc. 2020.
Copyright_xml	– notice: The Author(s), under exclusive licence to Springer Nature America, Inc. 2020 – notice: The Author(s), under exclusive licence to Springer Nature America, Inc. 2020.
DBID	AAYXX CITATION CGR CUY CVF ECM EIF NPM 3V. 7QL 7QP 7QR 7TK 7TM 7U9 7X7 7XB 88A 88E 88I 8AO 8FD 8FE 8FG 8FH 8FI 8FJ 8FK ABJCF ABUWG AEUYN AFKRA AZQEC BBNVY BENPR BGLVJ BHPHI BKSAR C1K CCPQU D1I DWQXO FR3 FYUFA GHDGH GNUQQ H94 HCIFZ K9. KB. LK8 M0S M1P M2P M7N M7P P64 PCBAR PDBOC PHGZM PHGZT PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI PRINS Q9U RC3 7X8 5PM
DOI	10.1038/s41589-020-0530-0
DatabaseName	CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed ProQuest Central (Corporate) Bacteriology Abstracts (Microbiology B) Calcium & Calcified Tissue Abstracts Chemoreception Abstracts Neurosciences Abstracts Nucleic Acids Abstracts Virology and AIDS Abstracts ProQuest Health & Medical Collection ProQuest Central (purchase pre-March 2016) Biology Database (Alumni Edition) Medical Database (Alumni Edition) Science Database (Alumni Edition) ProQuest Pharma Collection Technology Research Database ProQuest SciTech Collection ProQuest Technology Collection ProQuest Natural Science Collection Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) Materials Science & Engineering Collection ProQuest Central (Alumni) ProQuest One Sustainability ProQuest Central UK/Ireland ProQuest Central Essentials Biological Science Collection ProQuest Central Technology collection Natural Science Collection Earth, Atmospheric & Aquatic Science Collection Environmental Sciences and Pollution Management ProQuest One Community College ProQuest Materials Science Collection ProQuest Central Engineering Research Database Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student AIDS and Cancer Research Abstracts SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Materials Science Database Biological Sciences ProQuest Health & Medical Collection Medical Database ProQuest Central Science Database (via ProQuest) Algology Mycology and Protozoology Abstracts (Microbiology C) Biological Science Database Biotechnology and BioEngineering Abstracts Earth, Atmospheric & Aquatic Science Database Materials Science Collection ProQuest Central Premium ProQuest One Academic ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic (retired) ProQuest One Academic UKI Edition ProQuest Central China ProQuest Central Basic Genetics Abstracts MEDLINE - Academic PubMed Central (Full Participant titles)
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) ProQuest Central Student ProQuest Central Essentials Nucleic Acids Abstracts SciTech Premium Collection ProQuest Central China Environmental Sciences and Pollution Management ProQuest One Applied & Life Sciences ProQuest One Sustainability Health Research Premium Collection Natural Science Collection Health & Medical Research Collection Biological Science Collection Chemoreception Abstracts ProQuest Central (New) ProQuest Medical Library (Alumni) Virology and AIDS Abstracts ProQuest Science Journals (Alumni Edition) ProQuest Biological Science Collection ProQuest One Academic Eastern Edition Earth, Atmospheric & Aquatic Science Database ProQuest Hospital Collection ProQuest Technology Collection Health Research Premium Collection (Alumni) Biological Science Database Neurosciences Abstracts ProQuest Hospital Collection (Alumni) Biotechnology and BioEngineering Abstracts ProQuest Health & Medical Complete ProQuest One Academic UKI Edition Engineering Research Database ProQuest One Academic Calcium & Calcified Tissue Abstracts ProQuest One Academic (New) Technology Collection Technology Research Database ProQuest One Academic Middle East (New) Materials Science Collection ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) ProQuest One Community College ProQuest One Health & Nursing ProQuest Natural Science Collection ProQuest Pharma Collection ProQuest Biology Journals (Alumni Edition) ProQuest Central Earth, Atmospheric & Aquatic Science Collection ProQuest Health & Medical Research Collection Genetics Abstracts Health and Medicine Complete (Alumni Edition) ProQuest Central Korea Bacteriology Abstracts (Microbiology B) Algology Mycology and Protozoology Abstracts (Microbiology C) AIDS and Cancer Research Abstracts Materials Science Database ProQuest Materials Science Collection ProQuest Central Basic ProQuest Science Journals ProQuest SciTech Collection ProQuest Medical Library Materials Science & Engineering Collection ProQuest Central (Alumni) MEDLINE - Academic
DatabaseTitleList	MEDLINE ProQuest Central Student MEDLINE - Academic ProQuest Central Student
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Anatomy & Physiology Chemistry
EISSN	1552-4469
EndPage	782
ExternalDocumentID	PMC7556716 32367018 10_1038_s41589_020_0530_0
Genre	Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural
GrantInformation_xml	– fundername: MEXT \| Japan Society for the Promotion of Science (JSPS) grantid: JP17J09439 funderid: https://doi.org/10.13039/501100001691 – fundername: U.S. Department of Health & Human Services \| National Institutes of Health (NIH) grantid: GM068524; GM095970 funderid: https://doi.org/10.13039/100000002 – fundername: Ministry of Education, Culture, Sports, Science and Technology (MEXT) grantid: JP17H05432 funderid: https://doi.org/10.13039/501100001700 – fundername: U.S. Department of Health & Human Services \| National Institutes of Health (NIH) – fundername: NIGMS NIH HHS grantid: R01 GM095970 – fundername: NIGMS NIH HHS grantid: K12 GM068524 – fundername: NIGMS NIH HHS grantid: K99 GM129454
GroupedDBID	--- 0R~ 123 29M 39C 3V. 4.4 53G 5BI 70F 7X7 88A 88E 88I 8AO 8FE 8FG 8FH 8FI 8FJ 8R4 8R5 AAEEF AARCD AAYZH AAZLF ABAWZ ABDBF ABJCF ABJNI ABLJU ABUWG ACBWK ACGFS ACGOD ACIWK ACPRK ACUHS ADBBV AENEX AEUYN AFANA AFBBN AFKRA AFRAH AFSHS AGAYW AGHTU AHBCP AHMBA AHOSX AHSBF AIBTJ ALFFA ALIPV ALMA_UNASSIGNED_HOLDINGS ARMCB ASPBG AVWKF AXYYD AZFZN AZQEC BBNVY BENPR BGLVJ BHPHI BKKNO BKSAR BPHCQ BVXVI CCPQU CS3 CZ9 D1I DB5 DU5 DWQXO EBS EE. EJD EMOBN ESX EXGXG F5P FEDTE FQGFK FSGXE FYUFA GNUQQ HCIFZ HMCUK HVGLF HZ~ KB. KC. LK5 LK8 M0L M1P M2P M7P M7R NACWA NNMJJ O9- ODYON P2P PCBAR PDBOC PQQKQ PROAC PSQYO Q2X RNT RNTTT SHXYY SIXXV SJN SNYQT SOJ SV3 TAOOD TBHMF TDRGL TSG TUS UKHRP ~8M AAYXX ABFSG ACSTC AEZWR AFFHD AFHIU AGSTI AHWEU AIXLP ALPWD ATHPR CITATION PHGZM PHGZT PJZUB PPXIY PQGLB CGR CUY CVF ECM EIF NFIDA NPM 7QL 7QP 7QR 7TK 7TM 7U9 7XB 8FD 8FK C1K FR3 H94 K9. M7N P64 PKEHL PQEST PQUKI PRINS Q9U RC3 7X8 PUEGO 5PM
ID	FETCH-LOGICAL-c564t-67ade9a85f057d70b0284bd5adf424eac588a6fd35427f8e5a03662cfa482a7e3
IEDL.DBID	M7P
ISICitedReferencesCount	42
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000530218800004&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	1552-4450 1552-4469
IngestDate	Tue Nov 04 01:52:46 EST 2025 Thu Sep 04 18:01:31 EDT 2025 Mon Oct 06 16:54:27 EDT 2025 Mon Oct 06 16:52:15 EDT 2025 Thu Apr 03 06:59:17 EDT 2025 Tue Nov 18 22:33:30 EST 2025 Sat Nov 29 02:45:19 EST 2025 Fri Feb 21 02:39:44 EST 2025
IsDoiOpenAccess	false
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	7
Language	English
License	Reprints and permissions information is available at www.nature.com/reprints.
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c564t-67ade9a85f057d70b0284bd5adf424eac588a6fd35427f8e5a03662cfa482a7e3
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Author contributions Y.K., M.D.B. and D.D. designed the research. T.D.D. synthesized the chemical probes. The crystallization of the proteins was done by D.D. The X-ray diffraction experiment was carried out by Y.K. and D.D. The experimental phasing was done by Y.K. Refinement and validation of the structure was done by D.D., Y.K. and S.F. Site-directed mutagenesis and analysis of mutants were done by D.D. and M.H. The cross-linked complex was prepared by D.D. and A.C. D.D. and Y.K. wrote the draft manuscript. A.C., T.D.D., M.D.B., S.F. and Y.O. commented on the draft. Y.K. and Y.O. finalized the manuscript and all authors approved it. Y.K., M.D.B. and Y.O. directed the research.
ORCID	0000-0001-5629-7075 0000-0002-4472-2254 0000-0003-4905-5320 0000-0003-1346-6435 0000-0002-9143-7392
OpenAccessLink	https://www.ncbi.nlm.nih.gov/pmc/articles/7556716
PMID	32367018
PQID	2415570255
PQPubID	29034
PageCount	7
ParticipantIDs	pubmedcentral_primary_oai_pubmedcentral_nih_gov_7556716 proquest_miscellaneous_2398622104 proquest_journals_2476776216 proquest_journals_2415570255 pubmed_primary_32367018 crossref_primary_10_1038_s41589_020_0530_0 crossref_citationtrail_10_1038_s41589_020_0530_0 springer_journals_10_1038_s41589_020_0530_0
PublicationCentury	2000
PublicationDate	2020-07-01
PublicationDateYYYYMMDD	2020-07-01
PublicationDate_xml	– month: 07 year: 2020 text: 2020-07-01 day: 01
PublicationDecade	2020
PublicationPlace	New York
PublicationPlace_xml	– name: New York – name: United States – name: Cambridge
PublicationTitle	Nature chemical biology
PublicationTitleAbbrev	Nat Chem Biol
PublicationTitleAlternate	Nat Chem Biol
PublicationYear	2020
Publisher	Nature Publishing Group US Nature Publishing Group
Publisher_xml	– name: Nature Publishing Group US – name: Nature Publishing Group
References	Moche, Schneider, Edwards, Dehesh, Lindqvist (CR17) 1999; 274 Worthington, Burkart (CR29) 2006; 4 Klaus, Grininger (CR1) 2018; 35 Nanson, Himiari, Swarbrick, Forwood (CR15) 2015; 5 Finzel, Lee, Burkart (CR18) 2015; 16 Crosby, Crump (CR19) 2012; 29 Miyanaga, Iwasawa, Shinohara, Kudo, Eguchi (CR22) 2016; 113 Hertweck (CR3) 2009; 48 Hertweck, Luzhetskyy, Rebets, Bechthold (CR4) 2007; 24 Du (CR8) 2016; 17 Evans, Murshudov (CR34) 2013; 69 Vagin (CR38) 2004; 60 Shen (CR12) 2009; 19 Staunton, Weissman (CR2) 2001; 18 Adams (CR39) 2010; 66 Chen, Re, Burkart (CR21) 2018; 35 Tsai (CR6) 2018; 87 Trajtenberg (CR13) 2014; 281 Keatinge-Clay, Maltby, Medzihradszky, Khosla, Stroud (CR11) 2004; 11 Wang (CR14) 2006; 441 Clarke, Mercer, La Clair, Burkart (CR30) 2005; 127 Miyanaga (CR23) 2018; 140 Vagin, Teplyakov (CR35) 2010; 66 Worthington, Rivera, Torpey, Alexander, Burkart (CR28) 2006; 1 Dodge (CR26) 2019; 116 (CR40) 1994; 50 Zhang, Hurlbert, White, Rock (CR16) 2006; 281 Kabsch (CR33) 2010; 66 Du, Katsuyama, Shin-Ya, Ohnishi (CR9) 2018; 57 Das, Khosla (CR5) 2009; 42 Shakya (CR20) 2014; 136 Herbst (CR27) 2018; 14 Dreier, Khosla (CR7) 2000; 39 Grammbitter (CR10) 2019; 141 Worthington (CR32) 2008; 9 Kelley, Mezulis, Yates, Wass, Sternberg (CR36) 2015; 10 Nguyen (CR24) 2014; 505 Milligan (CR25) 2019; 15 Haushalter, Worthington, Hur, Burkart (CR31) 2008; 18 Emsley, Lohkamp, Scott, Cowtan (CR37) 2010; 66 HC Shen (530_CR12) 2009; 19 A Miyanaga (530_CR23) 2018; 140 LA Kelley (530_CR36) 2015; 10 D Du (530_CR9) 2018; 57 JC Milligan (530_CR25) 2019; 15 S-C Tsai (530_CR6) 2018; 87 D Du (530_CR8) 2016; 17 C Hertweck (530_CR3) 2009; 48 Y-M Zhang (530_CR16) 2006; 281 J Staunton (530_CR2) 2001; 18 G Shakya (530_CR20) 2014; 136 AS Worthington (530_CR29) 2006; 4 C Hertweck (530_CR4) 2007; 24 J Dreier (530_CR7) 2000; 39 PR Evans (530_CR34) 2013; 69 P Emsley (530_CR37) 2010; 66 A Miyanaga (530_CR22) 2016; 113 K Finzel (530_CR18) 2015; 16 J Crosby (530_CR19) 2012; 29 W Kabsch (530_CR33) 2010; 66 GLC Grammbitter (530_CR10) 2019; 141 J Wang (530_CR14) 2006; 441 RW Haushalter (530_CR31) 2008; 18 A Das (530_CR5) 2009; 42 DA Herbst (530_CR27) 2018; 14 GJ Dodge (530_CR26) 2019; 116 AS Worthington (530_CR32) 2008; 9 AT Keatinge-Clay (530_CR11) 2004; 11 KM Clarke (530_CR30) 2005; 127 F Trajtenberg (530_CR13) 2014; 281 JD Nanson (530_CR15) 2015; 5 M Moche (530_CR17) 1999; 274 PD Adams (530_CR39) 2010; 66 M Klaus (530_CR1) 2018; 35 AS Worthington (530_CR28) 2006; 1 C Nguyen (530_CR24) 2014; 505 A Vagin (530_CR35) 2010; 66 A Chen (530_CR21) 2018; 35 AA Vagin (530_CR38) 2004; 60 Collaborative Computational Project, Number 4. (530_CR40) 1994; 50
References_xml	– volume: 15 start-page: 669 year: 2019 end-page: 671 ident: CR25 article-title: Molecular basis for interactions between an acyl carrier protein and a ketosynthase publication-title: Nat. Chem. Biol. doi: 10.1038/s41589-019-0301-y – volume: 35 start-page: 1070 year: 2018 end-page: 1081 ident: CR1 article-title: Engineering strategies for rational polyketide synthase design publication-title: Nat. Prod. Rep. doi: 10.1039/C8NP00030A – volume: 35 start-page: 1029 year: 2018 end-page: 1045 ident: CR21 article-title: Type II fatty acid and polyketide synthases: deciphering protein-protein and protein-substrate interactions publication-title: Nat. Prod. Rep. doi: 10.1039/C8NP00040A – volume: 39 start-page: 2088 year: 2000 end-page: 2095 ident: CR7 article-title: Mechanistic analysis of a type II polyketide synthase. Role of conserved residues in the β-ketoacyl synthase-chain length factor heterodimer publication-title: Biochemistry doi: 10.1021/bi992121l – volume: 281 start-page: 17390 year: 2006 end-page: 17399 ident: CR16 article-title: Roles of the active site water, histidine 303, and phenylalanine 396 in the catalytic mechanism of the elongation condensing enzyme of publication-title: J. Biol. Chem. doi: 10.1074/jbc.M513199200 – volume: 141 start-page: 16615 year: 2019 end-page: 16623 ident: CR10 article-title: An uncommon type II PKS catalyzes biosynthesis of aryl polyene pigments publication-title: J. Am. Chem. Soc. doi: 10.1021/jacs.8b10776 – volume: 136 start-page: 16792 year: 2014 end-page: 16799 ident: CR20 article-title: Modeling linear and cyclic PKS intermediates through atom replacement publication-title: J. Am. Chem. Soc. doi: 10.1021/ja5064857 – volume: 69 start-page: 1204 year: 2013 end-page: 1214 ident: CR34 article-title: How good are my data and what is the resolution? publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444913000061 – volume: 60 start-page: 2184 year: 2004 end-page: 2195 ident: CR38 article-title: REFMAC5 dictionary: organization of prior chemical knowledge and guidelines for its use publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444904023510 – volume: 50 start-page: 760 year: 1994 end-page: 763 ident: CR40 article-title: The CCP4 suite: programs for protein crystallography publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444994003112 – volume: 24 start-page: 162 year: 2007 end-page: 190 ident: CR4 article-title: Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork publication-title: Nat. Prod. Rep. doi: 10.1039/B507395M – volume: 16 start-page: 528 year: 2015 end-page: 547 ident: CR18 article-title: Using modern tools to probe the structure-function relationship of fatty acid synthases publication-title: Chembiochem doi: 10.1002/cbic.201402578 – volume: 87 start-page: 503 year: 2018 end-page: 531 ident: CR6 article-title: The structural enzymology of iterative aromatic polyketide synthases: a critical comparison with fatty acid synthases publication-title: Annu. Rev. Biochem. doi: 10.1146/annurev-biochem-063011-164509 – volume: 505 start-page: 427 year: 2014 end-page: 431 ident: CR24 article-title: Trapping the dynamic acyl carrier protein in fatty acid biosynthesis publication-title: Nature doi: 10.1038/nature12810 – volume: 9 start-page: 2096 year: 2008 end-page: 2103 ident: CR32 article-title: Probing the compatibility of type II ketosynthase-carrier protein partners publication-title: Chembiochem doi: 10.1002/cbic.200800198 – volume: 29 start-page: 1111 year: 2012 end-page: 1137 ident: CR19 article-title: The structural role of the carrier protein–active controller or passive carrier publication-title: Nat. Prod. Rep. doi: 10.1039/c2np20062g – volume: 4 start-page: 44 year: 2006 end-page: 46 ident: CR29 article-title: One-pot chemo-enzymatic synthesis of reporter-modified proteins publication-title: Org. Biomol. Chem. doi: 10.1039/B512735A – volume: 66 start-page: 125 year: 2010 end-page: 132 ident: CR33 article-title: XDS publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444909047337 – volume: 66 start-page: 22 year: 2010 end-page: 25 ident: CR35 article-title: Molecular replacement with MOLREP publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444909042589 – volume: 17 start-page: 1464 year: 2016 end-page: 1471 ident: CR8 article-title: Production of a novel amide-containing polyene by activating a cryptic biosynthetic gene cluster in sp. MSC090213JE08 publication-title: ChemBioChem doi: 10.1002/cbic.201600167 – volume: 140 start-page: 7970 year: 2018 end-page: 7978 ident: CR23 article-title: Structural basis of protein-protein interactions between a trans-acting acyltransferase and acyl carrier protein in polyketide disorazole biosynthesis publication-title: J. Am. Chem. Soc. doi: 10.1021/jacs.8b04162 – volume: 14 start-page: 474 year: 2018 end-page: 479 ident: CR27 article-title: The structural organization of substrate loading in iterative polyketide synthases publication-title: Nat. Chem. Biol. doi: 10.1038/s41589-018-0026-3 – volume: 10 start-page: 845 year: 2015 end-page: 858 ident: CR36 article-title: The Phyre2 web portal for protein modeling, prediction and analysis publication-title: Nat. Protoc. doi: 10.1038/nprot.2015.053 – volume: 66 start-page: 213 year: 2010 end-page: 221 ident: CR39 article-title: PHENIX: a comprehensive Python-based system for macromolecular structure solution publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444909052925 – volume: 274 start-page: 6031 year: 1999 end-page: 6034 ident: CR17 article-title: Structure of the complex between the antibiotic cerulenin and its target, β-ketoacyl-acyl carrier protein synthase publication-title: J. Biol. Chem. doi: 10.1074/jbc.274.10.6031 – volume: 127 start-page: 11234 year: 2005 end-page: 11235 ident: CR30 article-title: In vivo reporter labeling of proteins via metabolic delivery of coenzyme A analogues publication-title: J. Am. Chem. Soc. doi: 10.1021/ja052911k – volume: 116 start-page: 6775 year: 2019 end-page: 6783 ident: CR26 article-title: Structural and dynamical rationale for fatty acid unsaturation in publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1818686116 – volume: 66 start-page: 486 year: 2010 end-page: 501 ident: CR37 article-title: Features and development of Coot publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444910007493 – volume: 57 start-page: 1954 year: 2018 end-page: 1957 ident: CR9 article-title: Reconstitution of a type II polyketide synthase that catalyzes polyene formation publication-title: Angew. Chem. Int. Ed. Engl. doi: 10.1002/anie.201709636 – volume: 113 start-page: 1802 year: 2016 end-page: 1807 ident: CR22 article-title: Structure-based analysis of the molecular interactions between acyltransferase and acyl carrier protein in vicenistatin biosynthesis publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1520042113 – volume: 281 start-page: 2324 year: 2014 end-page: 2338 ident: CR13 article-title: Structural insights into bacterial resistance to cerulenin publication-title: FEBS J. doi: 10.1111/febs.12785 – volume: 48 start-page: 4688 year: 2009 end-page: 4716 ident: CR3 article-title: The biosynthetic logic of polyketide diversity publication-title: Angew. Chem. Int. Ed. Engl. doi: 10.1002/anie.200806121 – volume: 441 start-page: 358 year: 2006 end-page: 361 ident: CR14 article-title: Platensimycin is a selective FabF inhibitor with potent antibiotic properties publication-title: Nature doi: 10.1038/nature04784 – volume: 18 start-page: 3039 year: 2008 end-page: 3042 ident: CR31 article-title: An orthogonal purification strategy for isolating crosslinked domains of modular synthases publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/j.bmcl.2008.01.026 – volume: 18 start-page: 380 year: 2001 end-page: 416 ident: CR2 article-title: Polyketide biosynthesis: a millennium review publication-title: Nat. Prod. Rep. doi: 10.1039/a909079g – volume: 19 start-page: 1623 year: 2009 end-page: 1627 ident: CR12 article-title: Synthesis and biological evaluation of platensimycin analogs publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/j.bmcl.2009.02.006 – volume: 5 year: 2015 ident: CR15 article-title: Structural characterisation of the beta-ketoacyl-acyl carrier protein synthases, FabF and FabH, of publication-title: Sci. Rep. doi: 10.1038/srep14797 – volume: 42 start-page: 631 year: 2009 end-page: 639 ident: CR5 article-title: Biosynthesis of aromatic polyketides in bacteria publication-title: Acc. Chem. Res. doi: 10.1021/ar8002249 – volume: 11 start-page: 888 year: 2004 end-page: 893 ident: CR11 article-title: An antibiotic factory caught in action publication-title: Nat. Struct. Mol. Biol. doi: 10.1038/nsmb808 – volume: 1 start-page: 687 year: 2006 end-page: 691 ident: CR28 article-title: Mechanism-based protein cross-linking probes to investigate carrier protein-mediated biosynthesis publication-title: ACS Chem. Biol. doi: 10.1021/cb6003965 – volume: 66 start-page: 125 year: 2010 ident: 530_CR33 publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444909047337 – volume: 5 year: 2015 ident: 530_CR15 publication-title: Sci. Rep. doi: 10.1038/srep14797 – volume: 113 start-page: 1802 year: 2016 ident: 530_CR22 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1520042113 – volume: 42 start-page: 631 year: 2009 ident: 530_CR5 publication-title: Acc. Chem. Res. doi: 10.1021/ar8002249 – volume: 60 start-page: 2184 year: 2004 ident: 530_CR38 publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444904023510 – volume: 11 start-page: 888 year: 2004 ident: 530_CR11 publication-title: Nat. Struct. Mol. Biol. doi: 10.1038/nsmb808 – volume: 66 start-page: 486 year: 2010 ident: 530_CR37 publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444910007493 – volume: 24 start-page: 162 year: 2007 ident: 530_CR4 publication-title: Nat. Prod. Rep. doi: 10.1039/B507395M – volume: 141 start-page: 16615 year: 2019 ident: 530_CR10 publication-title: J. Am. Chem. Soc. doi: 10.1021/jacs.8b10776 – volume: 35 start-page: 1029 year: 2018 ident: 530_CR21 publication-title: Nat. Prod. Rep. doi: 10.1039/C8NP00040A – volume: 66 start-page: 213 year: 2010 ident: 530_CR39 publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444909052925 – volume: 441 start-page: 358 year: 2006 ident: 530_CR14 publication-title: Nature doi: 10.1038/nature04784 – volume: 10 start-page: 845 year: 2015 ident: 530_CR36 publication-title: Nat. Protoc. doi: 10.1038/nprot.2015.053 – volume: 281 start-page: 17390 year: 2006 ident: 530_CR16 publication-title: J. Biol. Chem. doi: 10.1074/jbc.M513199200 – volume: 127 start-page: 11234 year: 2005 ident: 530_CR30 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja052911k – volume: 16 start-page: 528 year: 2015 ident: 530_CR18 publication-title: Chembiochem doi: 10.1002/cbic.201402578 – volume: 48 start-page: 4688 year: 2009 ident: 530_CR3 publication-title: Angew. Chem. Int. Ed. Engl. doi: 10.1002/anie.200806121 – volume: 4 start-page: 44 year: 2006 ident: 530_CR29 publication-title: Org. Biomol. Chem. doi: 10.1039/B512735A – volume: 87 start-page: 503 year: 2018 ident: 530_CR6 publication-title: Annu. Rev. Biochem. doi: 10.1146/annurev-biochem-063011-164509 – volume: 69 start-page: 1204 year: 2013 ident: 530_CR34 publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444913000061 – volume: 57 start-page: 1954 year: 2018 ident: 530_CR9 publication-title: Angew. Chem. Int. Ed. Engl. doi: 10.1002/anie.201709636 – volume: 29 start-page: 1111 year: 2012 ident: 530_CR19 publication-title: Nat. Prod. Rep. doi: 10.1039/c2np20062g – volume: 14 start-page: 474 year: 2018 ident: 530_CR27 publication-title: Nat. Chem. Biol. doi: 10.1038/s41589-018-0026-3 – volume: 9 start-page: 2096 year: 2008 ident: 530_CR32 publication-title: Chembiochem doi: 10.1002/cbic.200800198 – volume: 1 start-page: 687 year: 2006 ident: 530_CR28 publication-title: ACS Chem. Biol. doi: 10.1021/cb6003965 – volume: 39 start-page: 2088 year: 2000 ident: 530_CR7 publication-title: Biochemistry doi: 10.1021/bi992121l – volume: 116 start-page: 6775 year: 2019 ident: 530_CR26 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1818686116 – volume: 505 start-page: 427 year: 2014 ident: 530_CR24 publication-title: Nature doi: 10.1038/nature12810 – volume: 281 start-page: 2324 year: 2014 ident: 530_CR13 publication-title: FEBS J. doi: 10.1111/febs.12785 – volume: 136 start-page: 16792 year: 2014 ident: 530_CR20 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja5064857 – volume: 18 start-page: 3039 year: 2008 ident: 530_CR31 publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/j.bmcl.2008.01.026 – volume: 17 start-page: 1464 year: 2016 ident: 530_CR8 publication-title: ChemBioChem doi: 10.1002/cbic.201600167 – volume: 15 start-page: 669 year: 2019 ident: 530_CR25 publication-title: Nat. Chem. Biol. doi: 10.1038/s41589-019-0301-y – volume: 50 start-page: 760 year: 1994 ident: 530_CR40 publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444994003112 – volume: 19 start-page: 1623 year: 2009 ident: 530_CR12 publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/j.bmcl.2009.02.006 – volume: 18 start-page: 380 year: 2001 ident: 530_CR2 publication-title: Nat. Prod. Rep. doi: 10.1039/a909079g – volume: 66 start-page: 22 year: 2010 ident: 530_CR35 publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444909042589 – volume: 35 start-page: 1070 year: 2018 ident: 530_CR1 publication-title: Nat. Prod. Rep. doi: 10.1039/C8NP00030A – volume: 140 start-page: 7970 year: 2018 ident: 530_CR23 publication-title: J. Am. Chem. Soc. doi: 10.1021/jacs.8b04162 – volume: 274 start-page: 6031 year: 1999 ident: 530_CR17 publication-title: J. Biol. Chem. doi: 10.1074/jbc.274.10.6031
SSID	ssj0036618
Score	2.5004132
Snippet	In type II polyketide synthases (PKSs), the ketosynthase–chain length factor (KS–CLF) complex catalyzes polyketide chain elongation with the acyl carrier... In type II polyketide synthases (PKSs), the ketosynthase-chain length factor (KS-CLF) complex catalyzes polyketide chain elongation with the acyl carrier...
SourceID	pubmedcentral proquest pubmed crossref springer
SourceType	Open Access Repository Aggregation Database Index Database Enrichment Source Publisher
StartPage	776
SubjectTerms	631/535/1266 631/92/60 631/92/607 Acyl carrier protein Acyl Carrier Protein - chemistry Acyl Carrier Protein - genetics Acyl Carrier Protein - metabolism Antifungal agents Biocatalysis Biochemical Engineering Biochemistry Bioorganic Chemistry Biosynthesis Catalytic Domain Cell Biology Chemistry Chemistry and Materials Science Chemistry/Food Science Cloning, Molecular Condensates Condensation Crosslinking Crystal structure Crystallography, X-Ray E coli Elongation Escherichia coli - enzymology Escherichia coli - genetics Escherichia coli Proteins - chemistry Escherichia coli Proteins - genetics Escherichia coli Proteins - metabolism Fatty Acid Synthases - chemistry Fatty Acid Synthases - genetics Fatty Acid Synthases - metabolism Fatty acids Fatty-acid synthase Gene Expression Genetic Vectors - chemistry Genetic Vectors - metabolism Models, Molecular Molecular interactions Molecular structure Mutagenesis Mutagenesis, Site-Directed Polyketide synthase Polyketide Synthases - chemistry Polyketide Synthases - genetics Polyketide Synthases - metabolism Polyketides - chemistry Polyketides - metabolism Protein Binding Protein Conformation, alpha-Helical Protein Conformation, beta-Strand Protein Interaction Domains and Motifs Protein Multimerization Proteins Recombinant Proteins - chemistry Recombinant Proteins - genetics Recombinant Proteins - metabolism Selectivity Site-directed mutagenesis Streptomyces - enzymology Streptomyces - genetics Substrate Specificity Substrates
Title	Structural basis for selectivity in a highly reducing type II polyketide synthase
URI	https://link.springer.com/article/10.1038/s41589-020-0530-0 https://www.ncbi.nlm.nih.gov/pubmed/32367018 https://www.proquest.com/docview/2415570255 https://www.proquest.com/docview/2476776216 https://www.proquest.com/docview/2398622104 https://pubmed.ncbi.nlm.nih.gov/PMC7556716
Volume	16
WOSCitedRecordID	wos000530218800004&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVPQU databaseName: Biological Science Database (ProQuest) customDbUrl: eissn: 1552-4469 dateEnd: 20211231 omitProxy: false ssIdentifier: ssj0036618 issn: 1552-4450 databaseCode: M7P dateStart: 20190101 isFulltext: true titleUrlDefault: http://search.proquest.com/biologicalscijournals providerName: ProQuest – providerCode: PRVPQU databaseName: Earth, Atmospheric & Aquatic Science Database customDbUrl: eissn: 1552-4469 dateEnd: 20211231 omitProxy: false ssIdentifier: ssj0036618 issn: 1552-4450 databaseCode: PCBAR dateStart: 20190101 isFulltext: true titleUrlDefault: https://search.proquest.com/eaasdb providerName: ProQuest – providerCode: PRVPQU databaseName: Health & Medical Collection (ProQuest) customDbUrl: eissn: 1552-4469 dateEnd: 20211231 omitProxy: false ssIdentifier: ssj0036618 issn: 1552-4450 databaseCode: 7X7 dateStart: 20190101 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: Materials Science Database (Proquest) customDbUrl: eissn: 1552-4469 dateEnd: 20211231 omitProxy: false ssIdentifier: ssj0036618 issn: 1552-4450 databaseCode: KB. dateStart: 20190101 isFulltext: true titleUrlDefault: http://search.proquest.com/materialsscijournals providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central customDbUrl: eissn: 1552-4469 dateEnd: 20211231 omitProxy: false ssIdentifier: ssj0036618 issn: 1552-4450 databaseCode: BENPR dateStart: 20190101 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest – providerCode: PRVPQU databaseName: Science Database (ProQuest) customDbUrl: eissn: 1552-4469 dateEnd: 20211231 omitProxy: false ssIdentifier: ssj0036618 issn: 1552-4450 databaseCode: M2P dateStart: 20190101 isFulltext: true titleUrlDefault: https://search.proquest.com/sciencejournals providerName: ProQuest
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3db9MwED-xDQle-Nj4CIzKSIgHUFjij9h5Qtu0iQmoyqf6FjmOo1UqaVkKUv977tykqEzbCy-WItuKrTvfne_OvwN4kebeu8SpuJTOxDI3ZWxllcZCJt5Z6Wweqih8_6CHQzMe56PO4dZ2aZW9TAyCupo58pEfcKkzjSc3zd7Of8ZUNYqiq10JjS3YIZQEEVL3Rr0kFqh7wlM4pXgspVpHNYU5aFFxUbIQp1CwwGZTL10yNi_nTP4TOA366PTu_-7kHtzpLFF2uGKd-3DDN7uwd9jgLfzHkr1kITc0ON134dZxXxduDz59CZCzBNfBUAdOWoZ2L2tDPZ1QiYJNGmYZ4SBPl-yCoGFxA4x8vezsjM1n0yW9s648a5fN4hy16AP4dnry9fhd3BVmiJ3K5CLOtK18bo2q0dqrdFKikSLLStmqllyiKFfG2KyuhJJc18YrS7TgrrbScKu9eAjbzazxj4HlFdepq9BsrEuJotb6sk50jZMkT2WqI0h6shSuQy2n4hnTIkTPhSlWlCyQkgVRskgieLWeMl9Bdlw3eL8nUtGd3rYgq0Zpum1d0d0TMILn626kAsVabONnv3CMyPGuiPdpGcGjFeesFyMCal5qItAbPLUeQJDfmz3N5DxAf2ulMk3_fd1z399lXbnHJ9dv4inc5uEcUA7yPmwjE_lncNP9XkzaiwFs6bEOrRnAztHJcPQZv94fvcH2Ix8Nwon7A5JuLT0
linkProvider	ProQuest
linkToHtml	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9QwEB6VglQuPFqggQJGAg5UURPHjp0DQlWh6qrLqoiCeguO7agrbZOlWUD5U_xGxs5m0VK1tx645GLn4fibhz3jbwBexpm1OtI8LJiWIctkESpm4jBhkdWKaZX5Kgpfh2I0kicn2dEK_O7Pwri0yl4nekVtau32yHcoE6lAyY3Td9Pvoasa5aKrfQmNDhaHtv2FS7bm7eA9zu8rSvc_HO8dhPOqAqHmKZuFqVDGZkryEl0VI6ICLSwrDFemZJShHuJSqrQ0CWdUlNJyhUo-pbpUTFIlbILPvQE30Y2g0qcKHvWaH7v5_UTHahYyxhdR1ETuNGgoXXISdaHnBC_LdvCCc3sxR_OfQK23f_t3_7c_dw_uzD1tstuJxn1YsdU6bOxWalafteQ18bmvPqiwDmt7fd27Dfj02VPqOjoSgjZ-3BD060nj6wX5ShtkXBFFHM_zpCXnjvoWfxhxe9lkMCDTetK6c-TGkqatZqfoJTyAL9cy0IewWtWV3QSSGSpibdAtLguGpkTZooxEiTcxGrNYBBD1MMj1nJXdFQeZ5D47IJF5h5wckZM75ORRAG8Wt0w7SpKrOm_1oMjn2qnJndfGhVtNXtLcAyaAF4tmnAUXS1KVrX9gnyTDtTDFxXwAjzqkLj4m8ayAsQxALGF40cFRmi-3VONTT20uOE-Fe-92j_a_n3XpGB9fPYjnsHZw_HGYDwejwydwm3oZdPnWW7CKgLJP4Zb-ORs358-8NBP4dt1C8Afp84Xs
linkToPdf	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9QwEB6VgoALj5ZHoICRgENRtIljx84BoaplxarVahEP9RYcx1FXWrJLs4Dy1_h1zHg3i5aqvfXAJRc7D8ffPOwZfwPwIs6cs5GVYSGsDkWmi9CIMg4TETlrhDWZr6Lw5UgNh_r4OBttwO_uLAylVXY60Svqcmppj7zHhUoVSm6c9qplWsTooP929j2kClIUae3KaSwgcujaX7h8a94MDnCuX3Lef_dp_324rDAQWpmKeZgqU7rMaFmh21KqqEBrK4pSmrISXKBOklqbtCoTKbiqtJMGFX7KbWWE5ka5BJ97Ba4qIi33aYOjzgpgN7-3SAxnoRByFVFNdK9Bo0mJSpzC0Ale1m3iGUf3bL7mP0Fbbwv7t__nv3gHbi09cLa3EJm7sOHqLdjeq818-q1lr5jPifXBhi24sd_Vw9uGDx891S7RlDC0_eOGob_PGl9HyFfgYOOaGUb8z5OWnRIlLv48RnvcbDBgs-mkpfPlpWNNW89P0Hu4B58vZaD3YbOe1u4hsKzkKrYlustVIdDEGFdUkarwJsFjEasAog4SuV2ytVPRkEnuswYSnS9QlCOKckJRHgWwu7pltqAquajzTgeQfKm1mpy8OalolXlOcweeAJ6vmnEWKMZkajf9gX2SDNfIHBf5ATxYoHb1MYlnC4x1AGoNz6sORHW-3lKPTzzluZIyVfTe1x3y_37WuWN8dPEgnsF1xH5-NBgePoab3IsjpWHvwCbiyT2Ba_bnfNycPvWCzeDrZcvAHynLjqk
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Structural+basis+for+selectivity+in+a+highly+reducing+type+II+polyketide+synthase&rft.jtitle=Nature+chemical+biology&rft.au=Du%2C+Danyao&rft.au=Katsuyama%2C+Yohei&rft.au=Horiuchi%2C+Masanobu&rft.au=Fushinobu%2C+Shinya&rft.date=2020-07-01&rft.eissn=1552-4469&rft.volume=16&rft.issue=7&rft.spage=776&rft_id=info:doi/10.1038%2Fs41589-020-0530-0&rft_id=info%3Apmid%2F32367018&rft.externalDocID=32367018
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1552-4450&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1552-4450&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1552-4450&client=summon