Biocatalysis in Drug Design: Engineered Reductive Aminases (RedAms) Are Used to Access Chiral Building Blocks with Multiple Stereocenters

Novel building blocks are in constant demand during the search for innovative bioactive small molecule therapeutics by enabling the construction of structure–activity–property–toxicology relationships. Complex chiral molecules containing multiple stereocenters are an important component in compound...

Full description

Saved in:
Bibliographic Details
Published inJournal of the American Chemical Society Vol. 145; no. 40; pp. 22041 - 22046
Main Authors Casamajo, Arnau Rué, Yu, Yuqi, Schnepel, Christian, Morrill, Charlotte, Barker, Rhys, Levy, Colin W., Finnigan, James, Spelling, Victor, Westerlund, Kristina, Petchey, Mark, Sheppard, Robert J., Lewis, Richard J., Falcioni, Francesco, Hayes, Martin A., Turner, Nicholas J.
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 11.10.2023
Amer Chemical Soc
Subjects
Online AccessGet full text

Cover

Loading…
Abstract Novel building blocks are in constant demand during the search for innovative bioactive small molecule therapeutics by enabling the construction of structure–activity–property–toxicology relationships. Complex chiral molecules containing multiple stereocenters are an important component in compound library expansion but can be difficult to access by traditional organic synthesis. Herein, we report a biocatalytic process to access a specific diastereomer of a chiral amine building block used in drug discovery. A reductive aminase (RedAm) was engineered following a structure-guided mutagenesis strategy to produce the desired isomer. The engineered RedAm (IR-09 W204R) was able to generate the (S,S,S)-isomer 3 in 45% conversion and 95% ee from the racemic ketone 2. Subsequent palladium-catalyzed deallylation of 3 yielded the target primary amine 4 in a 73% yield. This engineered biocatalyst was used at preparative scale and represents a potential starting point for further engineering and process development.
AbstractList Novel building blocks are in constant demand during the search for innovative bioactive small molecule therapeutics by enabling the construction of structure–activity–property–toxicology relationships. Complex chiral molecules containing multiple stereocenters are an important component in compound library expansion but can be difficult to access by traditional organic synthesis. Herein, we report a biocatalytic process to access a specific diastereomer of a chiral amine building block used in drug discovery. A reductive aminase (RedAm) was engineered following a structure-guided mutagenesis strategy to produce the desired isomer. The engineered RedAm (IR-09 W204R) was able to generate the (S,S,S)-isomer 3 in 45% conversion and 95% ee from the racemic ketone 2. Subsequent palladium-catalyzed deallylation of 3 yielded the target primary amine 4 in a 73% yield. This engineered biocatalyst was used at preparative scale and represents a potential starting point for further engineering and process development.
Novel building blocks are in constant demand during the search for innovative bioactive small molecule therapeutics by enabling the construction of structure–activity–property–toxicology relationships. Complex chiral molecules containing multiple stereocenters are an important component in compound library expansion but can be difficult to access by traditional organic synthesis. Herein, we report a biocatalytic process to access a specific diastereomer of a chiral amine building block used in drug discovery. A reductive aminase (RedAm) was engineered following a structure-guided mutagenesis strategy to produce the desired isomer. The engineered RedAm (IR-09 W204R) was able to generate the ( S , S , S )-isomer 3 in 45% conversion and 95% ee from the racemic ketone 2 . Subsequent palladium-catalyzed deallylation of 3 yielded the target primary amine 4 in a 73% yield. This engineered biocatalyst was used at preparative scale and represents a potential starting point for further engineering and process development.
Author Yu, Yuqi
Hayes, Martin A.
Casamajo, Arnau Rué
Turner, Nicholas J.
Spelling, Victor
Finnigan, James
Schnepel, Christian
Lewis, Richard J.
Falcioni, Francesco
Westerlund, Kristina
Sheppard, Robert J.
Barker, Rhys
Levy, Colin W.
Petchey, Mark
Morrill, Charlotte
AuthorAffiliation Manchester Institute of Biotechnology
AlbaNova University Center
Medicinal Chemistry, Research and Early Development; Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D
Prozomix Ltd
Compound Synthesis and Management, Discovery Sciences, Biopharmaceuticals R&D
Early Chemical Development, Pharmaceutical Sciences, Biopharmaceuticals R&D
School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Industrial Biotechnology, KTH Royal Institute of Technology
AstraZeneca
Department of Medicinal Chemistry, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D
Department of Chemistry, University of Manchester
AuthorAffiliation_xml – name: AlbaNova University Center
– name: Department of Medicinal Chemistry, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D
– name: Department of Chemistry, University of Manchester
– name: Compound Synthesis and Management, Discovery Sciences, Biopharmaceuticals R&D
– name: Manchester Institute of Biotechnology
– name: Prozomix Ltd
– name: Medicinal Chemistry, Research and Early Development; Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D
– name: AstraZeneca
– name: School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Industrial Biotechnology, KTH Royal Institute of Technology
– name: Early Chemical Development, Pharmaceutical Sciences, Biopharmaceuticals R&D
Author_xml – sequence: 1
  givenname: Arnau Rué
  orcidid: 0000-0001-8932-8763
  surname: Casamajo
  fullname: Casamajo, Arnau Rué
  organization: Manchester Institute of Biotechnology
– sequence: 2
  givenname: Yuqi
  surname: Yu
  fullname: Yu, Yuqi
  organization: Manchester Institute of Biotechnology
– sequence: 3
  givenname: Christian
  orcidid: 0000-0002-4331-2675
  surname: Schnepel
  fullname: Schnepel, Christian
  organization: AlbaNova University Center
– sequence: 4
  givenname: Charlotte
  surname: Morrill
  fullname: Morrill, Charlotte
  organization: Manchester Institute of Biotechnology
– sequence: 5
  givenname: Rhys
  surname: Barker
  fullname: Barker, Rhys
  organization: Manchester Institute of Biotechnology
– sequence: 6
  givenname: Colin W.
  surname: Levy
  fullname: Levy, Colin W.
  organization: Manchester Institute of Biotechnology
– sequence: 7
  givenname: James
  surname: Finnigan
  fullname: Finnigan, James
  organization: Prozomix Ltd
– sequence: 8
  givenname: Victor
  orcidid: 0000-0001-5976-8047
  surname: Spelling
  fullname: Spelling, Victor
  organization: AstraZeneca
– sequence: 9
  givenname: Kristina
  surname: Westerlund
  fullname: Westerlund, Kristina
  organization: Medicinal Chemistry, Research and Early Development; Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D
– sequence: 10
  givenname: Mark
  surname: Petchey
  fullname: Petchey, Mark
  organization: AstraZeneca
– sequence: 11
  givenname: Robert J.
  surname: Sheppard
  fullname: Sheppard, Robert J.
  organization: Medicinal Chemistry, Research and Early Development; Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D
– sequence: 12
  givenname: Richard J.
  orcidid: 0000-0001-9404-8520
  surname: Lewis
  fullname: Lewis, Richard J.
  organization: AstraZeneca
– sequence: 13
  givenname: Francesco
  surname: Falcioni
  fullname: Falcioni, Francesco
  organization: AstraZeneca
– sequence: 14
  givenname: Martin A.
  orcidid: 0000-0002-2640-8464
  surname: Hayes
  fullname: Hayes, Martin A.
  organization: AstraZeneca
– sequence: 15
  givenname: Nicholas J.
  orcidid: 0000-0002-8708-0781
  surname: Turner
  fullname: Turner, Nicholas J.
  email: Nicholas.Turner@manchester.ac.uk
  organization: Manchester Institute of Biotechnology
BackLink https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-338791$$DView record from Swedish Publication Index
BookMark eNqNkd1uEzEQhS1URNPCHQ_gyyLY4p_dtZcbtEnKj1SEBJRby_FONk43drC9jfoIvDWOEhVV4oKrkT3fOTOjc4ZOnHeA0EtKLilh9O1am3jJDRGEkidoQitGioqy-gRNCCGsELLmp-gsxnV-lkzSZ-iUCyGZlGyCfk-tNzrp4T7aiK3D8zD2eA7R9u4dvnK9dQABOvwNutEkewe43VinI0R8kf_aTXyF2wD4JmYoedwaAzHi2coGPeDpaIfOuh5PB29uI97ZtMJfxiHZ7QD4e8rW3oDLNT5HT5d6iPDiWM_RzYerH7NPxfXXj59n7XWhS85T0REwJRMlFdAI3fFGLMq6Etp0rK51p-tlZ3QlF42ghvJaCtOwrhSmJiXRpBb8HBUH37iD7bhQ22A3Otwrr62a25-t8qFXt2mlOJeioZl_f-AzvIFuv22-7JHsccfZler9naKkEpRIkh0ujg7B_xohJrWx0cAwaAd-jIpJwahoSsYz-uaAmuBjDLB8mEOJ2set9nGrY9wZlwd8Bwu_jMaCM_AgIRkRNa1onZMndGaTTta7mR9dytLX_y_9e8J--tqPweWI_r3TH6n9zcE
CitedBy_id crossref_primary_10_1038_s42004_024_01211_5
crossref_primary_10_1002_anie_202402316
crossref_primary_10_1039_D3NP90052E
crossref_primary_10_1002_ange_202402316
crossref_primary_10_1021_jacsau_4c00284
Cites_doi 10.1126/sciadv.aay9320
10.1016/j.cbpa.2017.09.008
10.1016/j.drudis.2020.09.027
10.1021/jacs.2c08285
10.1021/acscatal.6b00782
10.1002/cctc.201402218
10.1021/acs.jnatprod.9b01285
10.1021/acs.joc.8b02867
10.1038/s41586-022-04458-x
10.1002/adsc.201801326
10.1039/d1sc04471k
10.1039/d0sc02253e
10.1002/anie.201708408
10.1002/cctc.201500605
10.1002/anie.202014931
10.1038/s41929-019-0385-5
10.1002/cctc.201701408
10.1016/j.bmc.2021.116562
10.1021/acsmedchemlett.2c00124
10.1021/acscatal.2c06066
10.1126/science.1188934
10.1021/jacs.2c07143
10.1021/acscatal.8b03491
10.1021/jacsau.2c00712
10.1016/j.cbpa.2010.02.001
10.1021/acssensors.7b00223
10.1021/acs.jmedchem.0c00754
10.1039/d1ra08053a
10.1038/s41929-019-0341-4
10.1002/anie.201404560
10.1038/s41929-021-00671-5
10.1021/cr500399p
10.1002/cctc.201500764
10.1021/acs.jmedchem.5b01409
10.1016/j.cbpa.2020.01.012
10.1038/s41557-020-00606-w
10.3390/catal11121466
10.1038/s41570-018-0055-1
10.1038/s41586-022-04422-9
10.1021/jacsau.2c00415
10.1002/adsc.201900424
10.1016/j.drudis.2018.10.016
10.1021/jacs.1c12106
10.1126/science.abo5590
10.1126/science.abn2009
10.1039/D1RA08053A
10.1039/D1SC04471K
10.1038/nchem.2782
ContentType Journal Article
Copyright 2023 The Authors. Published by American Chemical Society
2023 The Authors. Published by American Chemical Society 2023 The Authors
Copyright_xml – notice: 2023 The Authors. Published by American Chemical Society
– notice: 2023 The Authors. Published by American Chemical Society 2023 The Authors
DBID 1KM
BLEPL
BNZSX
DTL
AAYXX
CITATION
7X8
5PM
ADTPV
AFDQA
AOWAS
D8T
D8V
ZZAVC
DOI 10.1021/jacs.3c07010
DatabaseName Index Chemicus
Web of Science Core Collection
Web of Science - Science Citation Index Expanded - 2023
Science Citation Index Expanded
CrossRef
MEDLINE - Academic
PubMed Central (Full Participant titles)
SwePub
SWEPUB Kungliga Tekniska Högskolan full text
SwePub Articles
SWEPUB Freely available online
SWEPUB Kungliga Tekniska Högskolan
SwePub Articles full text
DatabaseTitle Web of Science
CrossRef
MEDLINE - Academic
DatabaseTitleList

Web of Science

Database_xml – sequence: 1
  dbid: 1KM
  name: Index Chemicus
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/woscc/search-with-editions?editions=WOS.IC
  sourceTypes:
    Enrichment Source
    Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Chemistry
EISSN 1520-5126
EndPage 22046
ExternalDocumentID oai_DiVA_org_kth_338791
10_1021_jacs_3c07010
001076151600001
b145862448
GrantInformation_xml – fundername: EPSRC; UK Research & Innovation (UKRI); Engineering & Physical Sciences Research Council (EPSRC)
– fundername: BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC)
– fundername: AstraZeneca
  grantid: EP/S005226/1
– fundername: European Research Council (ERC); Spanish Government
  grantid: GRANTS:17016081; 742987
– fundername: ERC; European Research Council (ERC)
  grantid: 742987
– fundername: ;
  grantid: 742987
– fundername: ;
  grantid: EP/S005226/1
– fundername: ;
  grantid: NA
GroupedDBID ---
-DZ
-ET
-~X
.DC
.K2
4.4
55A
5GY
5RE
5VS
7~N
85S
AABXI
ABFRP
ABHMW
ABMVS
ABPPZ
ABPTK
ABQRX
ABUCX
ACGFO
ACGFS
ACJ
ACNCT
ACS
ADHLV
AEESW
AENEX
AFEFF
AGHSJ
AGXLV
AHGAQ
ALMA_UNASSIGNED_HOLDINGS
AQSVZ
BAANH
BKOMP
CS3
DU5
EBS
ED~
F5P
GGK
GNL
IH2
IH9
JG~
LG6
P2P
ROL
RXW
TAE
TAF
TN5
UHB
UI2
UKR
UPT
VF5
VG9
VQA
W1F
WH7
XSW
YQT
YZZ
ZCA
~02
1KM
53G
AAHBH
ABJNI
ACBEA
BLEPL
CUPRZ
DTL
GROUPED_WOS_SCIENCE_CITATION_INDEX_EXPANDED
AAYXX
CITATION
7X8
5PM
.GJ
.HR
186
1WB
3EH
3O-
41~
6TJ
AAUPJ
AAYJJ
AAYOK
ABDEX
ABTAH
ABWLT
ACBNA
ACKIV
ADTPV
AFDQA
AFFDN
AFFNX
AI.
AIDAL
ANTXH
AOWAS
D0S
D8T
D8V
EJD
IHE
MVM
NHB
OHT
P-O
RNS
UBC
UBX
UQL
VH1
X7L
XOL
YXA
YXE
YYP
ZCG
ZE2
ZGI
ZHY
ZY4
ZZAVC
ID FETCH-LOGICAL-a433t-d0ec427417e97ad397b4657acd266ada6fdca58b971c13687c92d47c6040a0673
IEDL.DBID ACS
ISICitedReferencesCount 5
ISICitedReferencesURI https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestApp=WOS&DestLinkType=CitingArticles&UT=001076151600001
ISSN 0002-7863
1520-5126
IngestDate Tue Oct 01 22:48:55 EDT 2024
Tue Sep 17 21:29:30 EDT 2024
Sat Aug 17 00:30:38 EDT 2024
Fri Dec 06 01:33:45 EST 2024
Wed Sep 18 08:07:17 EDT 2024
Fri Dec 13 17:48:26 EST 2024
Thu Oct 12 04:47:38 EDT 2023
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 40
Keywords CHEMISTRY
AMINATION
AMINES
DIVERSE
DISCOVERY
Language English
License https://creativecommons.org/licenses/by/4.0
Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
LinkModel DirectLink
LogoURL https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg
MergedId FETCHMERGED-LOGICAL-a433t-d0ec427417e97ad397b4657acd266ada6fdca58b971c13687c92d47c6040a0673
Notes European Research Council (ERC)
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ORCID 0000-0001-8932-8763
0000-0002-2640-8464
0000-0001-5976-8047
0000-0002-8708-0781
0000-0001-9404-8520
0000-0002-4331-2675
OpenAccessLink https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-338791
PMID 37782882
PQID 2872179423
PQPubID 23479
PageCount 6
ParticipantIDs proquest_miscellaneous_2872179423
pubmedcentral_primary_oai_pubmedcentral_nih_gov_10571080
acs_journals_10_1021_jacs_3c07010
swepub_primary_oai_DiVA_org_kth_338791
webofscience_primary_001076151600001CitationCount
crossref_primary_10_1021_jacs_3c07010
webofscience_primary_001076151600001
PublicationCentury 2000
PublicationDate 2023-10-11
PublicationDateYYYYMMDD 2023-10-11
PublicationDate_xml – month: 10
  year: 2023
  text: 2023-10-11
  day: 11
PublicationDecade 2020
PublicationPlace WASHINGTON
PublicationPlace_xml – name: WASHINGTON
PublicationTitle Journal of the American Chemical Society
PublicationTitleAbbrev J AM CHEM SOC
PublicationTitleAlternate J. Am. Chem. Soc
PublicationYear 2023
Publisher American Chemical Society
Amer Chemical Soc
Publisher_xml – name: American Chemical Society
– name: Amer Chemical Soc
References Huber, T (WOS:000340574600017) 2014; 6
Brow, DG (WOS:000376840600003) 2016; 59
Zumbrägel, N (WOS:000457947800031) 2019; 84
Volochnyuk, DM (WOS:000461263200006) 2019; 24
Harawa, V (WOS:000884854300001) 2022; 144
Devine, PN (WOS:000452215000005) 2018; 2
Kumar, R (WOS:000697659700007) 2021; 4
Sharma, M (WOS:000453491100053) 2018; 8
Romero, E (WOS:000626167700001) 2021; 60
Schober, M (WOS:000489769600015) 2019; 2
Yao, PY (WOS:000457795500024) 2019; 361
Fryszkowska, A (WOS:000534347400021) 2020; 55
Gilio, AK (WOS:000928704000001) 2023
Pessatti, TB (WOS:000743658200001) 2021; 11
Ertl, P (WOS:000771035100004) 2022; 54
Husain, SM (WOS:000342678200019) 2014; 53
Athavale, SV (WOS:000866246300001) 2022
Arnold, Frances H (MEDLINE:29064156) 2018; 57
Boutureira, O (WOS:000351187400004) 2015; 115
Scheller, PN (WOS:000362909200006) 2015; 7
Saldívar-González, FI (WOS:000733544900001) 2022; 13
McIntosh, JA (WOS:000769827000017) 2022; 603
France, SP (WOS:000424674000005) 2018; 10
Tomberg, A (WOS:000595879900011) 2020; 25
Newman, DJ (WOS:000526306000025) 2020; 83
Thorpe, TW (WOS:000779100400020) 2022; 604
Hendrick, CE (WOS:000820778600001) 2022
Labonté, JM (WOS:000783316500025) 2022; 376
Rodríguez, DF (WOS:000741554200001) 2022; 12
Conradt, D (WOS:000362553100006) 2015; 7
Adams, JP (WOS:000471070400005) 2019; 361
Young, RJ (WOS:000875538300001) 2022; 2
Montgomery, SL (WOS:000537235300008) 2020; 6
Aleku, GA (WOS:000377326700060) 2016; 6
Bauer, RA (WOS:000279216500004) 2010; 14
Benkovics, T (WOS:000789021900024) 2022; 144
Savile, CK (WOS:000279925900036) 2010; 329
Ertl, P (WOS:000562941200031) 2020; 63
Grogan, G (WOS:000428488200005) 2018; 43
Chen, K (WOS:000508320900001) 2020; 3
(001076151600001.45) 2022
Mangas-Sanchez, J (WOS:000536688300021) 2020; 11
France, SP (WOS:000939521500001) 2023; 3
Shang, X (WOS:000406829300014) 2017; 2
Marshall, JR (WOS:000603955500002) 2021; 13
ref9/cit9
ref45/cit45
ref6/cit6
ref36/cit36
ref3/cit3
ref27/cit27
ref18/cit18
ref11/cit11
ref25/cit25
ref16/cit16
ref29/cit29
ref32/cit32
ref23/cit23
ref39/cit39
ref14/cit14
ref8/cit8
ref5/cit5
ref31/cit31
ref2/cit2
ref43/cit43
ref34/cit34
ref37/cit37
ref28/cit28
ref40/cit40
ref20/cit20
ref17/cit17
ref10/cit10
ref26/cit26
ref35/cit35
ref19/cit19
ref21/cit21
ref12/cit12
ref15/cit15
ref42/cit42
ref41/cit41
ref22/cit22
ref13/cit13
ref33/cit33
ref4/cit4
ref30/cit30
ref1/cit1
ref24/cit24
ref38/cit38
ref44/cit44
ref7/cit7
References_xml – volume: 6
  start-page: ARTN eaay9320
  year: 2020
  ident: WOS:000537235300008
  article-title: Characterization of imine reductases in reductive amination for the exploration of structure-activity relationships
  publication-title: SCIENCE ADVANCES
  doi: 10.1126/sciadv.aay9320
  contributor:
    fullname: Montgomery, SL
– volume: 43
  start-page: 15
  year: 2018
  ident: WOS:000428488200005
  article-title: Synthesis of chiral amines using redox biocatalysis
  publication-title: CURRENT OPINION IN CHEMICAL BIOLOGY
  doi: 10.1016/j.cbpa.2017.09.008
  contributor:
    fullname: Grogan, G
– volume: 25
  start-page: 2174
  year: 2020
  ident: WOS:000595879900011
  article-title: Can easy chemistry produce complex, diverse, and novel molecules?
  publication-title: DRUG DISCOVERY TODAY
  doi: 10.1016/j.drudis.2020.09.027
  contributor:
    fullname: Tomberg, A
– year: 2022
  ident: WOS:000866246300001
  article-title: Enzymatic Nitrogen Insertion into Unactivated C-H Bonds
  publication-title: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
  doi: 10.1021/jacs.2c08285
  contributor:
    fullname: Athavale, SV
– volume: 6
  start-page: 3880
  year: 2016
  ident: WOS:000377326700060
  article-title: Stereoselectivity and Structural Characterization of an Irvine Reductase (IRED) from Amycolatopsis orientalis
  publication-title: ACS CATALYSIS
  doi: 10.1021/acscatal.6b00782
  contributor:
    fullname: Aleku, GA
– volume: 6
  start-page: 2248
  year: 2014
  ident: WOS:000340574600017
  article-title: Direct Reductive Amination of Ketones: Structure and Activity of S-Selective Imine Reductases from Streptomyces
  publication-title: CHEMCATCHEM
  doi: 10.1002/cctc.201402218
  contributor:
    fullname: Huber, T
– volume: 83
  start-page: 770
  year: 2020
  ident: WOS:000526306000025
  article-title: Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019
  publication-title: JOURNAL OF NATURAL PRODUCTS
  doi: 10.1021/acs.jnatprod.9b01285
  contributor:
    fullname: Newman, DJ
– volume: 84
  start-page: 1440
  year: 2019
  ident: WOS:000457947800031
  article-title: Enantioselective Biocatalytic Reduction of 2H-1,4-Benzoxazines Using Imine Reductases
  publication-title: JOURNAL OF ORGANIC CHEMISTRY
  doi: 10.1021/acs.joc.8b02867
  contributor:
    fullname: Zumbrägel, N
– volume: 604
  start-page: 86
  year: 2022
  ident: WOS:000779100400020
  article-title: Multifunctional biocatalyst for conjugate reduction and reductive amination
  publication-title: NATURE
  doi: 10.1038/s41586-022-04458-x
  contributor:
    fullname: Thorpe, TW
– volume: 361
  start-page: 556
  year: 2019
  ident: WOS:000457795500024
  article-title: Imine Reductase-Catalyzed Enantioselective Reduction of Bulky α,β-Unsaturated Imines en Route to a Pharmaceutically Important Morphinan Skeleton
  publication-title: ADVANCED SYNTHESIS & CATALYSIS
  doi: 10.1002/adsc.201801326
  contributor:
    fullname: Yao, PY
– volume: 13
  start-page: 1526
  year: 2022
  ident: WOS:000733544900001
  article-title: Natural product drug discovery in the artificial intelligence era
  publication-title: CHEMICAL SCIENCE
  doi: 10.1039/d1sc04471k
  contributor:
    fullname: Saldívar-González, FI
– volume: 11
  start-page: 5052
  year: 2020
  ident: WOS:000536688300021
  article-title: Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases
  publication-title: CHEMICAL SCIENCE
  doi: 10.1039/d0sc02253e
  contributor:
    fullname: Mangas-Sanchez, J
– volume: 57
  start-page: 4143
  year: 2018
  ident: MEDLINE:29064156
  article-title: Directed Evolution: Bringing New Chemistry to Life.
  publication-title: Angewandte Chemie (International ed. in English)
  doi: 10.1002/anie.201708408
  contributor:
    fullname: Arnold, Frances H
– volume: 7
  start-page: 3116
  year: 2015
  ident: WOS:000362553100006
  article-title: Diversity in Reduction with Short-Chain Dehydrogenases: Tetrahydroxynaphthalene Reductase, Trihydroxynaphthalene Reductase, and Glucose Dehydrogenase
  publication-title: CHEMCATCHEM
  doi: 10.1002/cctc.201500605
  contributor:
    fullname: Conradt, D
– volume: 60
  start-page: 16824
  year: 2021
  ident: WOS:000626167700001
  article-title: Enzymatic Late-Stage Modifications: Better Late Than Never
  publication-title: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
  doi: 10.1002/anie.202014931
  contributor:
    fullname: Romero, E
– volume: 3
  start-page: 203
  year: 2020
  ident: WOS:000508320900001
  article-title: Engineering new catalytic activities in enzymes
  publication-title: NATURE CATALYSIS
  doi: 10.1038/s41929-019-0385-5
  contributor:
    fullname: Chen, K
– volume: 10
  start-page: 510
  year: 2018
  ident: WOS:000424674000005
  article-title: Identification of Novel Bacterial Members of the Imine Reductase Enzyme Family that Perform Reductive Amination
  publication-title: CHEMCATCHEM
  doi: 10.1002/cctc.201701408
  contributor:
    fullname: France, SP
– volume: 54
  start-page: ARTN 116562
  year: 2022
  ident: WOS:000771035100004
  article-title: Substituents of life: The most common substituent patterns present in natural products
  publication-title: BIOORGANIC & MEDICINAL CHEMISTRY
  doi: 10.1016/j.bmc.2021.116562
  contributor:
    fullname: Ertl, P
– year: 2022
  ident: WOS:000820778600001
  article-title: Direct-to-Biology Accelerates PROTAC Synthesis and the Evaluation of Linker Effects on Permeability and Degradation
  publication-title: ACS MEDICINAL CHEMISTRY LETTERS
  doi: 10.1021/acsmedchemlett.2c00124
  contributor:
    fullname: Hendrick, CE
– start-page: 1669
  year: 2023
  ident: WOS:000928704000001
  article-title: A Reductive Aminase Switches to Imine Reductase Mode for a Bulky Amine Substrate
  publication-title: ACS CATALYSIS
  doi: 10.1021/acscatal.2c06066
  contributor:
    fullname: Gilio, AK
– volume: 329
  start-page: 305
  year: 2010
  ident: WOS:000279925900036
  article-title: Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin Manufacture
  publication-title: SCIENCE
  doi: 10.1126/science.1188934
  contributor:
    fullname: Savile, CK
– volume: 144
  start-page: 21088
  year: 2022
  ident: WOS:000884854300001
  article-title: Synthesis of Stereoenriched Piperidines via Chemo-Enzymatic Dearomatization of Activated Pyridines
  publication-title: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
  doi: 10.1021/jacs.2c07143
  contributor:
    fullname: Harawa, V
– volume: 8
  start-page: 11534
  year: 2018
  ident: WOS:000453491100053
  article-title: A Mechanism for Reductive Amination Catalyzed by Fungal Reductive Aminases
  publication-title: ACS CATALYSIS
  doi: 10.1021/acscatal.8b03491
  contributor:
    fullname: Sharma, M
– volume: 3
  start-page: 715
  year: 2023
  ident: WOS:000939521500001
  article-title: The Evolving Nature of Biocatalysis in Pharmaceutical Research and Development
  publication-title: JACS AU
  doi: 10.1021/jacsau.2c00712
  contributor:
    fullname: France, SP
– volume: 14
  start-page: 308
  year: 2010
  ident: WOS:000279216500004
  article-title: Expanding the range of 'druggable' targets with natural product-based libraries: an academic perspective
  publication-title: CURRENT OPINION IN CHEMICAL BIOLOGY
  doi: 10.1016/j.cbpa.2010.02.001
  contributor:
    fullname: Bauer, RA
– volume: 2
  start-page: 961
  year: 2017
  ident: WOS:000406829300014
  article-title: Fluorescent Protein-Based Turn-On Probe through a General Protection-Deprotection Design Strategy
  publication-title: ACS SENSORS
  doi: 10.1021/acssensors.7b00223
  contributor:
    fullname: Shang, X
– volume: 63
  start-page: 8408
  year: 2020
  ident: WOS:000562941200031
  article-title: The Most Common Functional Groups in Bioactive Molecules and How Their Popularity Has Evolved over Time
  publication-title: JOURNAL OF MEDICINAL CHEMISTRY
  doi: 10.1021/acs.jmedchem.0c00754
  contributor:
    fullname: Ertl, P
– volume: 12
  start-page: 1932
  year: 2022
  ident: WOS:000741554200001
  article-title: Bio-click chemistry: a bridge between biocatalysis and click chemistry
  publication-title: RSC ADVANCES
  doi: 10.1039/d1ra08053a
  contributor:
    fullname: Rodríguez, DF
– volume: 2
  start-page: 909
  year: 2019
  ident: WOS:000489769600015
  article-title: Chiral synthesis of LSD1 inhibitor GSK2879552 enabled by directed evolution of an imine reductase
  publication-title: NATURE CATALYSIS
  doi: 10.1038/s41929-019-0341-4
  contributor:
    fullname: Schober, M
– volume: 53
  start-page: 9806
  year: 2014
  ident: WOS:000342678200019
  article-title: Unprecedented Role of Hydronaphthoquinone Tautomers in Biosynthesis
  publication-title: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
  doi: 10.1002/anie.201404560
  contributor:
    fullname: Husain, SM
– volume: 4
  start-page: 775
  year: 2021
  ident: WOS:000697659700007
  article-title: Biocatalytic reductive amination from discovery to commercial manufacturing applied to abrocitinib JAK1 inhibitor
  publication-title: NATURE CATALYSIS
  doi: 10.1038/s41929-021-00671-5
  contributor:
    fullname: Kumar, R
– volume: 115
  start-page: 2174
  year: 2015
  ident: WOS:000351187400004
  article-title: Advances in Chemical Protein Modification
  publication-title: CHEMICAL REVIEWS
  doi: 10.1021/cr500399p
  contributor:
    fullname: Boutureira, O
– volume: 7
  start-page: 3239
  year: 2015
  ident: WOS:000362909200006
  article-title: Imine Reductase-Catalyzed Intermolecular Reductive Amination of Aldehydes and Ketones
  publication-title: CHEMCATCHEM
  doi: 10.1002/cctc.201500764
  contributor:
    fullname: Scheller, PN
– volume: 59
  start-page: 4443
  year: 2016
  ident: WOS:000376840600003
  article-title: Analysis of Past and Present Synthetic Methodologies on Medicinal Chemistry: Where Have All the New Reactions Gone?
  publication-title: JOURNAL OF MEDICINAL CHEMISTRY
  doi: 10.1021/acs.jmedchem.5b01409
  contributor:
    fullname: Brow, DG
– volume: 55
  start-page: 151
  year: 2020
  ident: WOS:000534347400021
  article-title: Biocatalysis in drug discovery and development
  publication-title: CURRENT OPINION IN CHEMICAL BIOLOGY
  doi: 10.1016/j.cbpa.2020.01.012
  contributor:
    fullname: Fryszkowska, A
– volume: 13
  year: 2021
  ident: WOS:000603955500002
  article-title: Screening and characterization of a diverse panel of metagenomic imine reductases for biocatalytic reductive amination
  publication-title: NATURE CHEMISTRY
  doi: 10.1038/s41557-020-00606-w
  contributor:
    fullname: Marshall, JR
– volume: 11
  start-page: ARTN 1466
  year: 2021
  ident: WOS:000743658200001
  article-title: Protein Modifications: From Chemoselective Probes to Novel Biocatalysts
  publication-title: CATALYSTS
  doi: 10.3390/catal11121466
  contributor:
    fullname: Pessatti, TB
– volume: 2
  start-page: 409
  year: 2018
  ident: WOS:000452215000005
  article-title: Extending the application of biocatalysis to meet the challenges of drug development
  publication-title: NATURE REVIEWS CHEMISTRY
  doi: 10.1038/s41570-018-0055-1
  contributor:
    fullname: Devine, PN
– year: 2022
  ident: 001076151600001.45
  publication-title: AutoDockVina DocumentationRelease 1.2.0
– volume: 603
  start-page: 439
  year: 2022
  ident: WOS:000769827000017
  article-title: A kinase-cGAS cascade to synthesize a therapeutic STING activator
  publication-title: NATURE
  doi: 10.1038/s41586-022-04422-9
  contributor:
    fullname: McIntosh, JA
– volume: 2
  start-page: 2400
  year: 2022
  ident: WOS:000875538300001
  article-title: The Time and Place for Nature in Drug Discovery
  publication-title: JACS AU
  doi: 10.1021/jacsau.2c00415
  contributor:
    fullname: Young, RJ
– volume: 361
  start-page: 2421
  year: 2019
  ident: WOS:000471070400005
  article-title: Biocatalysis: A Pharma Perspective
  publication-title: ADVANCED SYNTHESIS & CATALYSIS
  doi: 10.1002/adsc.201900424
  contributor:
    fullname: Adams, JP
– volume: 24
  start-page: 390
  year: 2019
  ident: WOS:000461263200006
  article-title: Evolution of commercially available compounds for HTS
  publication-title: DRUG DISCOVERY TODAY
  doi: 10.1016/j.drudis.2018.10.016
  contributor:
    fullname: Volochnyuk, DM
– volume: 144
  start-page: 5855
  year: 2022
  ident: WOS:000789021900024
  article-title: Diverse Catalytic Reactions for the Stereoselective Synthesis ofCyclic Dinucleotide MK-1454
  publication-title: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
  doi: 10.1021/jacs.1c12106
  contributor:
    fullname: Benkovics, T
– volume: 376
  start-page: 138
  year: 2022
  ident: WOS:000783316500025
  article-title: There's more to RNA viruses than diseases
  publication-title: SCIENCE
  doi: 10.1126/science.abo5590
  contributor:
    fullname: Labonté, JM
– ident: ref23/cit23
  doi: 10.1038/s41586-022-04422-9
– ident: ref34/cit34
  doi: 10.1021/acscatal.8b03491
– ident: ref29/cit29
  doi: 10.1002/anie.201708408
– ident: ref30/cit30
  doi: 10.1021/acscatal.6b00782
– ident: ref14/cit14
  doi: 10.1016/j.cbpa.2020.01.012
– ident: ref31/cit31
  doi: 10.1021/acscatal.2c06066
– ident: ref42/cit42
  doi: 10.1002/cctc.201500605
– ident: ref18/cit18
  doi: 10.1016/j.bmc.2021.116562
– ident: ref8/cit8
  doi: 10.1002/anie.202014931
– ident: ref28/cit28
  doi: 10.1002/adsc.201801326
– ident: ref32/cit32
  doi: 10.1126/sciadv.aay9320
– ident: ref16/cit16
  doi: 10.1021/acs.jmedchem.5b01409
– ident: ref13/cit13
  doi: 10.1021/cr500399p
– ident: ref19/cit19
  doi: 10.1016/j.drudis.2018.10.016
– ident: ref4/cit4
  doi: 10.1038/s41929-021-00671-5
– ident: ref45/cit45
– ident: ref41/cit41
  doi: 10.1002/anie.201404560
– ident: ref26/cit26
  doi: 10.1016/j.cbpa.2010.02.001
– ident: ref24/cit24
  doi: 10.1021/acs.jmedchem.0c00754
– ident: ref9/cit9
  doi: 10.1021/acsmedchemlett.2c00124
– ident: ref10/cit10
  doi: 10.1126/science.abn2009
– ident: ref15/cit15
  doi: 10.1038/s41570-018-0055-1
– ident: ref6/cit6
  doi: 10.1126/science.1188934
– ident: ref11/cit11
  doi: 10.1039/D1RA08053A
– ident: ref3/cit3
  doi: 10.1038/s41586-022-04458-x
– ident: ref21/cit21
  doi: 10.1021/jacsau.2c00712
– ident: ref44/cit44
  doi: 10.1002/cctc.201500764
– ident: ref7/cit7
  doi: 10.1002/adsc.201900424
– ident: ref36/cit36
  doi: 10.1038/s41557-020-00606-w
– ident: ref39/cit39
  doi: 10.1021/jacs.2c07143
– ident: ref40/cit40
  doi: 10.1039/d0sc02253e
– ident: ref5/cit5
  doi: 10.1038/s41929-019-0341-4
– ident: ref12/cit12
  doi: 10.3390/catal11121466
– ident: ref17/cit17
  doi: 10.1039/D1SC04471K
– ident: ref43/cit43
  doi: 10.1002/cctc.201402218
– ident: ref2/cit2
  doi: 10.1021/jacs.2c08285
– ident: ref22/cit22
  doi: 10.1021/jacs.1c12106
– ident: ref37/cit37
  doi: 10.1038/nchem.2782
– ident: ref27/cit27
  doi: 10.1021/acs.jnatprod.9b01285
– ident: ref20/cit20
  doi: 10.1016/j.drudis.2020.09.027
– ident: ref25/cit25
  doi: 10.1021/jacsau.2c00415
– ident: ref33/cit33
  doi: 10.1016/j.cbpa.2017.09.008
– ident: ref35/cit35
  doi: 10.1021/acs.joc.8b02867
– ident: ref38/cit38
  doi: 10.1002/cctc.201701408
– ident: ref1/cit1
  doi: 10.1038/s41929-019-0385-5
SSID ssj0004281
Score 2.5082693
Snippet Novel building blocks are in constant demand during the search for innovative bioactive small molecule therapeutics by enabling the construction of...
Novel building blocks are in constant demand during the search for innovative bioactive small molecule therapeutics by enabling the construction of...
Source Web of Science
SourceID swepub
pubmedcentral
proquest
crossref
webofscience
acs
SourceType Open Access Repository
Aggregation Database
Enrichment Source
Index Database
Publisher
StartPage 22041
SubjectTerms Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
Title Biocatalysis in Drug Design: Engineered Reductive Aminases (RedAms) Are Used to Access Chiral Building Blocks with Multiple Stereocenters
URI http://dx.doi.org/10.1021/jacs.3c07010
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestApp=WOS&DestLinkType=FullRecord&UT=001076151600001
https://search.proquest.com/docview/2872179423
https://pubmed.ncbi.nlm.nih.gov/PMC10571080
https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-338791
Volume 145
WOS 001076151600001
WOSCitedRecordID wos001076151600001
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1Lb9QwELZQOcCFNyK0IFcqCA5Z1Y_YSW_ZLKVCKgfKot4ix_F2oxUJarKX_oP-6854ky67gOjVsS15PPZ8kxl_Q8iBMMpFRtjQMOVCqQ0Pi1lhQ9_IZlIUnkzn9Ks6mcov59H5OkF2O4LPkR_ItiNhQTXxJdV9rsHzRgiUna3fP_KYDTBXx0r0Ce7bo9EA2XbTAK1R5XZOZM8c-leD5I3P8WPyeXjCs8o5WYyWXTGyV38yOv5nXU_Iox5_0nSlME_JPVc_Iw-yoezbc3I9rhr_TwepSmhV08nl8oJOfKLHER3oC11JvyHpK16WNMV0mta19AO0pT_bjzC9o9MWOnUNTX1JRprNK1gwHfdluOkYrOiipfgfmJ72WY30DHbZNSgcQKUvyPT40_fsJOzrNYRGCtGF5aGzEulwtEu0KQHpFFJF2tgSUIApjZqV1kRxkWhmmVCxtgkvpbYKLhKDBXNekp26qd0rQg8Fn2mlYikjI7UWiXTMlUWEdXKiRBYB2Qfx5f15a3MfSufgymBrL9SAvBs2Ov-1ou74R7_9QQtykDUGTEztmmWbgzfJ8cLiIiDxhnrcTojs3Jtf6mruWbqxgDImcAbk_UqTNsZMqh9pDuqQL7p5LkSsExaQg9817bY7uu0agafyoZiAsLt0y3qKd6Q26F7fQVy75CEHAId2mbE9stNdLt0bAFxd8dafthubEyZK
link.rule.ids 230,314,780,784,885,2765,27076,27924,27925,56738,56788
linkProvider American Chemical Society
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1Lj9MwELbQclguvBFheXilBcEhq03s2Am3NGVVYNsDu0V7ixzHpVFFstqkF_4B_5oZ12lpBVKvjm0547Hns2f8DSEnTAkTKaZ9FQjjc6lCv5gV2reFwYyzwpLpjCdiNOVfrqNr91gd38LAIFroqbVO_A27ANIEQSHToKH4oOpuhNkqEQlll5tnkGEc9GhXxoK5OPfd1miHdLtthzbgcjc00hGI_tMuWRt0_oBM1qO3oSeL02VXnOpfO8SOe__eQ3LfoVGartTnEblj6sfkMOuTwD0hvwdVY294kLiEVjUd3i5_0KEN-_hIezJDU9JvSAGLWydNMbimNS19D2Xpz_YDdG_otIVKXUNTm6CRZvMK_psOXFJuOgCbumgp3grTsYtxpJcw56ZBGQFGfUqm55-uspHvsjf4ijPW-eWZ0RzJcaRJpCoB9xRcRFLpEjCBKpWYlVpFcZHIQAdMxFInYcmlFrCtKEyf84wc1E1tnhN6xsKZFCLmPFJcSpZwE5iyiDBrTpTwwiPHIL7crb42t471EA42WOqE6pG3_XznNysij__UO-6VIQdZo_tE1aZZtjmcLUPcvkLmkXhLS9YdIlf39pe6mlvObkynjOGcHnm3UqitNsPqe5qDSuSLbp4zFssk8MjJ3wq3ro6HeIkwVFjHjEeCfapljvAdiQ66F3uI6w05HF2NL_KLz5OvR-ReCNAOLXYQvCQH3e3SvAIo1hWv7QL8A_VPLrc
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1Lb9QwELaqIgEX3qgpL1cqCA6p6tixE27ZLKvyaIVaFvUWOY7DRqsmVZO98A_418x4ky27AqlcHduKx2PPZ8_4G0L2uZY21Nz4mknrC6UDPy9z47tCVgqeOzKd4xN5NBWfzsPzLcKGtzDwEy301DonPq7qy6LsGQaQKgg-cANaio-qboWw0WIUV5KeXT-FDCI2IF4VSd7Hum-2Rltk2nVbdA0wN8MjexLRv9omZ4cm98npagQu_GR-sOjyA_Nzg9zxv4b4gNzrUSlNlmr0kGzZ-hG5kw7J4B6TX6OqcTc9SGBCq5qOrxY_6NiFf7ynA6mhLegpUsHiFkoTDLJpbUvfQlly0b6D7i2dtlCpa2jiEjXSdFbB2OmoT85NR2Bb5y3F22F63Mc60jOYe9ugnACrPiHTyYdv6ZHfZ3HwteC884tDawSS5CgbK10A_smFDJU2BWADXWhZFkaHUR4rZhiXkTJxUAhlJGwvGtPoPCXbdVPbHUIPeVAqKSMhQi2U4rGwzBZ5iNlzwljkHtkD8WX9Kmwz52AP4ICDpb1QPfJ6mPPsckno8Y96e4NCZCBrdKPo2jaLNoMzZoDbWMA9Eq1pyqpD5Oxe_1JXM8fdjWmVMazTI2-WSrXWZlx9TzJQi2zezTLOIxUzj-z_qXSr6niYVwhHpXPQeITdpFraE78j4UG3ewNxvSK3v44n2ZePJ5-fkbsBIDw03Iw9J9vd1cK-AETW5S_dGvwNo_4xOg
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=Biocatalysis+in+Drug+Design%3A+Engineered+Reductive+Aminases+%28RedAms%29+Are+Used+to+Access+Chiral+Building+Blocks+with+Multiple+Stereocenters&rft.jtitle=Journal+of+the+American+Chemical+Society&rft.au=Casamajo%2C+Arnau+Ru%C3%A9&rft.au=Yu%2C+Yuqi&rft.au=Schnepel%2C+Christian&rft.au=Morrill%2C+Charlotte&rft.date=2023-10-11&rft.eissn=1520-5126&rft.volume=145&rft.issue=40&rft.spage=22041&rft.epage=22046&rft_id=info:doi/10.1021%2Fjacs.3c07010&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0002-7863&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0002-7863&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0002-7863&client=summon