Photoexcitation of flavoenzymes enables a stereoselective radical cyclization.

Tytuł:: Photoexcitation of flavoenzymes enables a stereoselective radical cyclization.
Autorzy:: Biegasiewicz KF; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Cooper SJ; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Gao X; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Oblinsky DG; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Kim JH; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Garfinkle SE; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Joyce LA; Department of Process Research and Development, Merck, Rahway, NJ 07065, USA.
Sandoval BA; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Scholes GD; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Hyster TK; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA. .
Źródło:: Science (New York, N.Y.) [Science] 2019 Jun 21; Vol. 364 (6446), pp. 1166-1169.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
Język:: English
Imprint Name(s):: Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-
MeSH Terms:: Biocatalysis/*radiation effects
FMN Reductase/*chemistry
FMN Reductase/*radiation effects
Cyclization ; Enzyme Activation ; Lactams/chemical synthesis ; Light ; Stereoisomerism
References:: Angew Chem Int Ed Engl. 2004 Nov 19;43(45):6032-40. (PMID: 15523680)
Nat Chem. 2018 Jul;10(7):770-775. (PMID: 29892028)
J Org Chem. 2016 Aug 19;81(16):6959-64. (PMID: 27442851)
Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55. (PMID: 15299926)
Phys Rev B Condens Matter. 1988 Jan 15;37(2):785-789. (PMID: 9944570)
Spectrochim Acta A Mol Biomol Spectrosc. 2010 Aug;76(3-4):418-22. (PMID: 20451442)
J Am Chem Soc. 2017 Aug 23;139(33):11313-11316. (PMID: 28780870)
Org Lett. 2018 Apr 20;20(8):2156-2159. (PMID: 29589943)
Org Lett. 2017 Mar 3;19(5):1144-1147. (PMID: 28212038)
Angew Chem Int Ed Engl. 2018 Jun 11;57(24):7240-7244. (PMID: 29689601)
Coord Chem Rev. 2012 Nov 1;256(21-22):2478-2487. (PMID: 23420049)
Angew Chem Int Ed Engl. 2016 Jan 4;55(1):58-102. (PMID: 26459814)
Biochemistry. 2015 Sep 1;54(34):5255-62. (PMID: 26230427)
Methods Mol Biol. 1999;131:9-23. (PMID: 10494539)
ACS Chem Biol. 2018 Aug 17;13(8):1914-1920. (PMID: 29905467)
J Med Chem. 2014 Dec 26;57(24):10257-74. (PMID: 25255204)
Front Plant Sci. 2018 Mar 20;9:357. (PMID: 29616068)
J Chem Phys. 2004 Mar 1;120(9):4281-8. (PMID: 15268597)
Nature. 2016 Dec 14;540(7633):414-417. (PMID: 27974767)
Science. 2016 May 27;352(6289):1078-82. (PMID: 27230373)
Nat Prod Rep. 2018 Feb 21;35(2):174-202. (PMID: 29417970)
ACS Catal. 2016 Jul 1;6(7):4286-4311. (PMID: 27398261)
Biochemistry. 1974 Jan 29;13(3):589-97. (PMID: 4149231)
Science. 2017 Sep 1;357(6354):903-907. (PMID: 28860382)
ACS Catal. 2019 May 15;8(4):3532-3549. (PMID: 31157123)
J Med Chem. 2014 Jan 23;57(2):477-94. (PMID: 24383452)
Biochemistry. 1966 Oct;5(10):3181-9. (PMID: 4382016)
Nat Chem Biol. 2013 May;9(5):285-8. (PMID: 23594772)
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32. (PMID: 20124692)
Chem Rev. 2016 Sep 14;116(17):10075-166. (PMID: 27285582)
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14. (PMID: 23793146)
Chem Rev. 2003 Jun;103(6):2203-37. (PMID: 12797829)
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674. (PMID: 19461840)
Chem Rev. 2003 Aug;103(8):3263-96. (PMID: 12914498)
Biochemistry. 1978 Jan 10;17(1):9-16. (PMID: 618550)
Nat Methods. 2009 May;6(5):343-5. (PMID: 19363495)
Grant Information:: P30 EB009998 United States EB NIBIB NIH HHS; P30 GM133893 United States GM NIGMS NIH HHS; P41 GM111244 United States GM NIGMS NIH HHS; R01 GM127703 United States GM NIGMS NIH HHS
Substance Nomenclature:: 0 (Lactams)
EC 1.5.1.38 (FMN Reductase)
Entry Date(s):: Date Created: 20190622 Date Completed: 20200406 Latest Revision: 20201222
Update Code:: 20240104
PubMed Central ID:: PMC7028431
DOI:: 10.1126/science.aaw1143
PMID:: 31221855
: Czasopismo naukowe

Pełny tekst

Photoexcitation is a common strategy for initiating radical reactions in chemical synthesis. We found that photoexcitation of flavin-dependent "ene"-reductases changes their catalytic function, enabling these enzymes to promote an asymmetric radical cyclization. This reactivity enables the construction of five-, six-, seven-, and eight-membered lactams with stereochemical preference conferred by the enzyme active site. After formation of a prochiral radical, the enzyme guides the delivery of a hydrogen atom from flavin-a challenging feat for small-molecule chemical reagents. The initial electron transfer occurs through direct excitation of an electron donor-acceptor complex that forms between the substrate and the reduced flavin cofactor within the enzyme active site. Photoexcitation of promiscuous flavoenzymes has thus furnished a previously unknown biocatalytic reaction.
(Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Zaloguj się, aby uzyskać dostęp do pełnego tekstu.

Informacja