{"id":"https://openalex.org/W3178657641","doi":"https://doi.org/10.1002/anie.202106938","title":"Asymmetric Alkylation of Ketones Catalyzed by Engineered TrpB","display_name":"Asymmetric Alkylation of Ketones Catalyzed by Engineered TrpB","publication_year":2021,"publication_date":"2021-07-16","ids":{"openalex":"https://openalex.org/W3178657641","doi":"https://doi.org/10.1002/anie.202106938","mag":"3178657641","pmid":"https://pubmed.ncbi.nlm.nih.gov/34269506","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/8440449"},"language":"en","primary_location":{"id":"doi:10.1002/anie.202106938","doi":"https://doi.org/10.1002/anie.202106938","is_oa":false,"landing_page_url":"https://doi.org/10.1002/anie.202106938","pdf_url":null,"source":{"id":"https://openalex.org/S67393510","display_name":"Angewandte Chemie International Edition","issn_l":"1433-7851","issn":["1433-7851","1521-3773"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Angewandte Chemie International Edition","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8440449","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5042493003","display_name":"Ella J. Watkins\u2010Dulaney","orcid":"https://orcid.org/0000-0002-0585-1598","observed_orcids":["https://orcid.org/0000-0002-0585-1598"]},"institutions":[{"id":"https://openalex.org/I122411786","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055","country_code":"US","type":"education","lineage":["https://openalex.org/I122411786"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ella J. Watkins\u2010Dulaney","raw_affiliation_strings":["Division of Biology and Biological Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA"],"raw_orcid":"https://orcid.org/0000-0002-0585-1598","affiliations":[{"raw_affiliation_string":"Division of Biology and Biological Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA","institution_ids":["https://openalex.org/I122411786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5028465253","display_name":"Noah P. Dunham","orcid":"https://orcid.org/0000-0001-8006-9566","observed_orcids":["https://orcid.org/0000-0001-8006-9566"]},"institutions":[{"id":"https://openalex.org/I122411786","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055","country_code":"US","type":"education","lineage":["https://openalex.org/I122411786"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Noah P. Dunham","raw_affiliation_strings":["Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA"],"raw_orcid":"https://orcid.org/0000-0001-8006-9566","affiliations":[{"raw_affiliation_string":"Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA","institution_ids":["https://openalex.org/I122411786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002074805","display_name":"Sabine Straathof","orcid":"https://orcid.org/0000-0002-6750-8349","observed_orcids":["https://orcid.org/0000-0002-6750-8349"]},"institutions":[{"id":"https://openalex.org/I122411786","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055","country_code":"US","type":"education","lineage":["https://openalex.org/I122411786"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sabine Straathof","raw_affiliation_strings":["Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA","institution_ids":["https://openalex.org/I122411786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050587367","display_name":"Soma Turi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I122411786","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055","country_code":"US","type":"education","lineage":["https://openalex.org/I122411786"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Soma Turi","raw_affiliation_strings":["Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA","institution_ids":["https://openalex.org/I122411786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5043841592","display_name":"Frances H. Arnold","orcid":"https://orcid.org/0000-0002-4027-364X","observed_orcids":["https://orcid.org/0000-0002-4027-364X"]},"institutions":[{"id":"https://openalex.org/I122411786","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055","country_code":"US","type":"education","lineage":["https://openalex.org/I122411786"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Frances H. Arnold","raw_affiliation_strings":["Division of Biology and Biological Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA","Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA"],"raw_orcid":"https://orcid.org/0000-0002-4027-364X","affiliations":[{"raw_affiliation_string":"Division of Biology and Biological Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA","institution_ids":["https://openalex.org/I122411786"]},{"raw_affiliation_string":"Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 210-41, 1200 E. California Boulevard, Pasadena, CA, 91125 USA","institution_ids":["https://openalex.org/I122411786"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5027030881","display_name":"Andrew R. Buller","orcid":"https://orcid.org/0000-0002-9635-4844","observed_orcids":["https://orcid.org/0000-0002-9635-4844"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Andrew R. Buller","raw_affiliation_strings":["Department of Chemistry University of Wisconsin\u2014Madison  1101 University Avenue Madison WI 53706 USA"],"raw_orcid":"https://orcid.org/0000-0002-9635-4844","affiliations":[{"raw_affiliation_string":"Department of Chemistry University of Wisconsin\u2014Madison  1101 University Avenue Madison WI 53706 USA","institution_ids":["https://openalex.org/I135310074"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5027030881","https://openalex.org/A5043841592"],"corresponding_institution_ids":["https://openalex.org/I122411786","https://openalex.org/I135310074"],"apc_list":{"value":5000,"currency":"USD","value_usd":5000},"apc_paid":null,"fwci":1.2874,"has_fulltext":false,"cited_by_count":32,"citation_normalized_percentile":{"value":0.795749,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":99},"biblio":{"volume":"60","issue":"39","first_page":"21412","last_page":"21417"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10404","display_name":"Enzyme Catalysis and Immobilization","score":0.9682999849319458,"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"}},"topics":[{"id":"https://openalex.org/T10404","display_name":"Enzyme Catalysis and Immobilization","score":0.9682999849319458,"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"}},{"id":"https://openalex.org/T10013","display_name":"Asymmetric Synthesis and Catalysis","score":0.027000000700354576,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T11281","display_name":"Asymmetric Hydrogenation and Catalysis","score":0.0012000000569969416,"subfield":{"id":"https://openalex.org/subfields/1604","display_name":"Inorganic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/trpb","display_name":"trpB","score":0.9580000042915344},{"id":"https://openalex.org/keywords/asymmetric-alkylation","display_name":"asymmetric alkylation","score":0.8550000190734863},{"id":"https://openalex.org/keywords/ketones","display_name":"ketones","score":0.8600000143051147},{"id":"https://openalex.org/keywords/protein-engineering","display_name":"protein engineering","score":0.5680000185966492},{"id":"https://openalex.org/keywords/directed-evolution","display_name":"directed evolution","score":0.9639999866485596},{"id":"https://openalex.org/keywords/propiophenone","display_name":"propiophenone","score":0.781000018119812},{"id":"https://openalex.org/keywords/enolates","display_name":"enolates","score":0.6790000200271606},{"id":"https://openalex.org/keywords/unnatural-amino-acids","display_name":"unnatural amino acids","score":0.8500000238418579},{"id":"https://openalex.org/keywords/stereocontrol","display_name":"stereocontrol","score":0.5170000195503235},{"id":"https://openalex.org/keywords/biocatalysis","display_name":"biocatalysis","score":0.6729999780654907}],"concepts":[{"id":"https://openalex.org/C164361826","wikidata":"https://www.wikidata.org/wiki/Q177604","display_name":"Alkylation","level":3,"score":0.7889617681503296},{"id":"https://openalex.org/C161790260","wikidata":"https://www.wikidata.org/wiki/Q82264","display_name":"Catalysis","level":2,"score":0.6379359364509583},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5364741683006287},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.373532772064209},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.3438032865524292},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.3093687891960144}],"mesh":[{"descriptor_ui":"D000478","descriptor_name":"Alkylation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007659","descriptor_name":"Ketones","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D007659","descriptor_name":"Ketones","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D014367","descriptor_name":"Tryptophan Synthase","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D014367","descriptor_name":"Tryptophan Synthase","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D015202","descriptor_name":"Protein Engineering","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015394","descriptor_name":"Molecular Structure","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055162","descriptor_name":"Biocatalysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1002/anie.202106938","doi":"https://doi.org/10.1002/anie.202106938","is_oa":false,"landing_page_url":"https://doi.org/10.1002/anie.202106938","pdf_url":null,"source":{"id":"https://openalex.org/S67393510","display_name":"Angewandte Chemie International Edition","issn_l":"1433-7851","issn":["1433-7851","1521-3773"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Angewandte Chemie International Edition","raw_type":"journal-article"},{"id":"pmid:34269506","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/34269506","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":"Angewandte Chemie (International ed. in English)","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:8440449","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8440449","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"Angew Chem Int Ed Engl","raw_type":"Text"},{"id":"pmh:oai:authors.library.caltech.edu:110068","doi":null,"is_oa":false,"landing_page_url":"https://authors.library.caltech.edu/110068/","pdf_url":null,"source":{"id":"https://openalex.org/S4306402161","display_name":"CaltechAUTHORS (California Institute of Technology)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I122411786","host_organization_name":"California Institute of Technology","host_organization_lineage":["https://openalex.org/I122411786"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Article"}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:8440449","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8440449","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"Angew Chem Int Ed Engl","raw_type":"Text"},"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G1059176983","display_name":"Prenylated-Flavin Enzymes as a new Platform for Drug Synthesis and Discovery","funder_award_id":"F32GM131620","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G289421598","display_name":"Engineering in vivo biomolecular synthesis with non-standard building blocks","funder_award_id":"1dp2gm137417-01","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G3070913743","display_name":null,"funder_award_id":"DP2-GM137417","funder_id":"https://openalex.org/F4320306080","funder_display_name":"Foundation for the National Institutes of Health"},{"id":"https://openalex.org/G4865625559","display_name":"Development of a Biocatalytic Platform for Convergent Synthesis of Chiral Amines","funder_award_id":"R01GM125887","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G5031693712","display_name":null,"funder_award_id":"DP2-GM137417","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"}],"funders":[{"id":"https://openalex.org/F4320306080","display_name":"Foundation for the National Institutes of Health","ror":"https://ror.org/00k86s890"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":28,"referenced_works":["https://openalex.org/W164048319","https://openalex.org/W1975177434","https://openalex.org/W1978424514","https://openalex.org/W1986551586","https://openalex.org/W1998495435","https://openalex.org/W2010602710","https://openalex.org/W2028828142","https://openalex.org/W2073914802","https://openalex.org/W2075854028","https://openalex.org/W2083631563","https://openalex.org/W2096044531","https://openalex.org/W2127694019","https://openalex.org/W2129133279","https://openalex.org/W2155528471","https://openalex.org/W2412082922","https://openalex.org/W2512006250","https://openalex.org/W2560971454","https://openalex.org/W2612673239","https://openalex.org/W2734128104","https://openalex.org/W2735805466","https://openalex.org/W2798059242","https://openalex.org/W2890944115","https://openalex.org/W2969221953","https://openalex.org/W2973016442","https://openalex.org/W2988704803","https://openalex.org/W3042340042","https://openalex.org/W4237751251","https://openalex.org/W4248539736"],"related_works":["https://openalex.org/W6940128243","https://openalex.org/W2988704803","https://openalex.org/W4386156221","https://openalex.org/W2588672439","https://openalex.org/W2969221953","https://openalex.org/W2799642058","https://openalex.org/W2735805466","https://openalex.org/W3091592280","https://openalex.org/W2465873216","https://openalex.org/W4416379413"],"abstract_inverted_index":{"The":[0,122],"\u03b2-subunit":[1],"of":[2,20,37,62,81,89,105,124,140],"tryptophan":[3],"synthase":[4],"(TrpB)":[5],"catalyzes":[6],"a":[7,86,133],"PLP-mediated":[8],"\u03b2-substitution":[9],"reaction":[10,56,127],"between":[11],"indole":[12],"and":[13,83,147],"serine":[14],"to":[15,25,57,76,128,143],"form":[16],"L-Trp.":[17],"A":[18],"succession":[19],"TrpB":[21,55,72,130],"protein":[22],"engineering":[23],"campaigns":[24],"expand":[26],"the":[27,34,54,59,78,97,103,112,115,129,138],"enzyme's":[28],"nucleophile":[29],"substrate":[30],"range":[31],"has":[32],"enabled":[33],"biocatalytic":[35],"production":[36],"diverse":[38],"non-canonical":[39,145],"amino":[40],"acids":[41],"(ncAAs).":[42],"Here,":[43],"we":[44],"show":[45],"that":[46,108],"ketone-derived":[47],"enolates":[48],"can":[49,119],"serve":[50],"as":[51],"nucleophiles":[52],"in":[53,67],"achieve":[58],"asymmetric":[60,79],"alkylation":[61,80],"ketones,":[63],"an":[64],"outstanding":[65],"challenge":[66],"synthetic":[68],"chemistry.":[69],"We":[70],"engineered":[71],"by":[73],"directed":[74],"evolution":[75],"catalyze":[77],"propiophenone":[82],"2-fluoroacetophenone":[84],"with":[85,93],"high":[87],"degree":[88],"selectivity.":[90],"In":[91],"reactions":[92],"propiophenone,":[94],"preference":[95],"for":[96],"opposite":[98],"product":[99],"diastereomer":[100],"emerges":[101],"over":[102,111],"course":[104],"evolution,":[106],"demonstrating":[107],"full":[109],"control":[110],"stereochemistry":[113],"at":[114],"new":[116,126],"chiral":[117],"center":[118],"be":[120],"achieved.":[121],"addition":[123],"this":[125],"platform":[131],"is":[132],"crucial":[134],"first":[135],"step":[136],"toward":[137],"development":[139],"efficient":[141],"methods":[142],"synthesize":[144],"prolines":[146],"other":[148],"chirally":[149],"dense":[150],"nitrogen":[151],"heterocycles.":[152]},"counts_by_year":[{"year":2026,"cited_by_count":7},{"year":2025,"cited_by_count":7},{"year":2024,"cited_by_count":8},{"year":2023,"cited_by_count":5},{"year":2022,"cited_by_count":4},{"year":2021,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2021-07-19T00:00:00"}