Structure, Function and Engineering of the Nonribosomal Peptide Synthetase Condensation Domain.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Peptide Synthases*/chemistry ; Peptide Synthases*/metabolism ; Peptide Synthases*/genetics ; Protein Engineering*/methods; Substrate Specificity ; Catalytic Domain ; Peptides/chemistry ; Peptides/metabolism ; Protein Domains

The nonribosomal peptide synthetase (NRPS) is a highly precise molecular assembly machinery for synthesizing structurally diverse peptides, which have broad medicinal applications. Withinthe NRPS, the condensation (C) domain is a core catalytic domain responsible for the formation of amide bonds between individual monomer residues during peptide elongation. This review summarizes various aspects of the C domain, including its structural characteristics, catalytic mechanisms, substrate specificity, substrate gating function, and auxiliary functions. Moreover, through case analyses of the NRPS engineering targeting the C domains, the vast potential of the C domain in the combinatorial biosynthesis of peptide natural product derivatives is demonstrated.

Acc Chem Res. 2008 Jan;41(1):4-10. (PMID: 17506516)
Nat Chem. 2018 Mar;10(3):282-287. (PMID: 29461527)
Synth Syst Biotechnol. 2022 Jun 10;7(3):989-1001. (PMID: 35782484)
Biotechnol J. 2020 Feb;15(2):e1900175. (PMID: 31520458)
Biochemistry. 2011 Jun 28;50(25):5668-79. (PMID: 21591693)
J Biol Chem. 1998 Aug 28;273(35):22773-81. (PMID: 9712910)
Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):275-80. (PMID: 16407157)
Angew Chem Int Ed Engl. 2017 Mar 27;56(14):3770-3821. (PMID: 28323366)
Chem Sci. 2017 Nov 1;8(11):7834-7843. (PMID: 29163920)
Appl Environ Microbiol. 2014 Sep;80(18):5723-31. (PMID: 25015884)
Cell Chem Biol. 2016 Apr 21;23(4):462-71. (PMID: 27105282)
Cell Chem Biol. 2016 Mar 17;23(3):331-9. (PMID: 26991102)
BMC Evol Biol. 2007 May 16;7:78. (PMID: 17506888)
Chem Biol. 2004 Jul;11(7):971-80. (PMID: 15271355)
Nat Prod Rep. 2023 Sep 20;40(9):1550-1582. (PMID: 37114973)
ACS Chem Biol. 2024 Mar 15;19(3):599-606. (PMID: 38395426)
J Nat Prod. 2020 Mar 27;83(3):770-803. (PMID: 32162523)
Nat Struct Biol. 2002 Jul;9(7):522-6. (PMID: 12055621)
Nat Chem Biol. 2024 Jun;20(6):761-769. (PMID: 38308044)
ACS Chem Biol. 2020 Jan 17;15(1):282-289. (PMID: 31887013)
Proc Natl Acad Sci U S A. 2000 May 23;97(11):5848-53. (PMID: 10811885)
J Am Chem Soc. 2016 Jun 1;138(21):6746-53. (PMID: 27213615)
Biochemistry. 2002 Jan 8;41(1):244-50. (PMID: 11772022)
Nat Commun. 2021 Jan 12;12(1):296. (PMID: 33436600)
Nat Commun. 2019 Jun 13;10(1):2613. (PMID: 31197182)
Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9259-64. (PMID: 24927540)
ACS Chem Biol. 2020 Jul 17;15(7):1808-1812. (PMID: 32608966)
Chem Sci. 2018 Oct 10;10(1):118-133. (PMID: 30713624)
ACS Omega. 2024 Jun 22;9(26):28556-28563. (PMID: 38973878)
Biochim Biophys Acta Proteins Proteom. 2017 Nov;1865(11 Pt B):1587-1604. (PMID: 28526268)
Nat Chem Biol. 2016 Dec;12(12):1001-1003. (PMID: 27748753)
Nat Prod Rep. 2021 Oct 20;38(10):1910-1937. (PMID: 34676836)
Biochemistry. 2000 May 16;39(19):5775-87. (PMID: 10801328)
Nat Prod Rep. 2015 May;32(5):641-53. (PMID: 25622971)
C R Acad Sci III. 1995 Sep;318(9):927-36. (PMID: 8521076)
Chem Biol. 2005 Nov;12(11):1189-200. (PMID: 16298298)
Chem Sci. 2020 Aug 24;11(35):9443-9458. (PMID: 34094211)
Nat Chem. 2018 Mar;10(3):275-281. (PMID: 29461518)
J Am Chem Soc. 2019 Oct 16;141(41):16222-16226. (PMID: 31573806)
Curr Res Struct Biol. 2020 Feb 05;2:14-24. (PMID: 34235466)
Nature. 2015 May 7;521(7550):105-9. (PMID: 25686610)
Biochemistry. 2002 Jul 23;41(29):9184-96. (PMID: 12119033)
Nat Commun. 2020 Sep 11;11(1):4554. (PMID: 32917865)
Proc Natl Acad Sci U S A. 2017 Jan 3;114(1):95-100. (PMID: 27994138)
ACS Synth Biol. 2012 Apr 20;1(4):118-29. (PMID: 22558529)
Nat Chem. 2019 Jul;11(7):653-661. (PMID: 31182822)
Cell Chem Biol. 2019 Nov 21;26(11):1526-1534.e2. (PMID: 31471217)
Biochim Biophys Acta. 2006 Sep;1758(9):1215-23. (PMID: 16615993)
Chem Sci. 2019 Aug 29;10(41):9466-9482. (PMID: 32055321)
J Am Chem Soc. 2010 May 5;132(17):6025-31. (PMID: 20387835)
Angew Chem Int Ed Engl. 2020 Aug 3;59(32):13463-13467. (PMID: 32329545)
Nat Chem Biol. 2015 Sep;11(9):660-70. (PMID: 26284673)
Nat Commun. 2021 May 4;12(1):2511. (PMID: 33947858)
J Mol Biol. 2013 Sep 9;425(17):3137-50. (PMID: 23756159)
Nat Commun. 2017 May 23;8:15349. (PMID: 28534477)
J Bacteriol. 1999 Jan;181(1):133-40. (PMID: 9864322)
PLoS One. 2014 Jan 21;9(1):e85667. (PMID: 24465643)
Angew Chem Int Ed Engl. 2014 Sep 15;53(38):10105-8. (PMID: 25081643)
Sci Rep. 2022 Mar 30;12(1):5353. (PMID: 35354859)
Science. 1999 Apr 16;284(5413):486-9. (PMID: 10205056)
Nat Chem Biol. 2012 Sep;8(9):791-7. (PMID: 22820420)
Structure. 2007 Jul;15(7):781-92. (PMID: 17637339)
Nat Chem Biol. 2024 Feb;20(2):251-260. (PMID: 37996631)
Synth Syst Biotechnol. 2022 Sep 20;7(4):1173-1180. (PMID: 36204332)
Chem Biol. 1997 Dec;4(12):927-37. (PMID: 9427658)
Nat Chem Biol. 2014 Apr;10(4):251-8. (PMID: 24531841)
Eur J Biochem. 2002 Jan;269(2):620-9. (PMID: 11856321)
Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15585-90. (PMID: 15498872)
Biochemistry. 2001 Jul 31;40(30):9023-31. (PMID: 11467965)
Nat Prod Rep. 2023 Jan 25;40(1):62-88. (PMID: 35796260)
Chem Biol. 2012 Feb 24;19(2):188-98. (PMID: 22365602)
Chem Biol. 2008 Feb;15(2):118-27. (PMID: 18291316)
ACS Chem Biol. 2017 Jul 21;12(7):1813-1819. (PMID: 28505407)
Nat Chem Biol. 2012 Oct;8(10):823-30. (PMID: 22902615)
Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1442-52. (PMID: 24816112)
Biochemistry. 2003 Aug 19;42(32):9722-30. (PMID: 12911314)
ACS Infect Dis. 2022 Jan 14;8(1):1-28. (PMID: 34878254)
Biochemistry. 2003 Oct 21;42(41):12095-104. (PMID: 14556641)
Angew Chem Int Ed Engl. 2021 Aug 2;60(32):17531-17538. (PMID: 34015175)

2018YFA0903004) National key research and development program of China; 2023J121 Natural Science Foundation of Ningbo City; LQ14C050001 Natural Science Foundation of Zhejiang Province; K.C. Wong Magna Fund at Ningbo University

Keywords: functional diversity of the condensation domains; nonribosomal peptide synthetase condensation domain; nonribosomal peptide synthetase engineering targeting the condensation domain

EC 6.3.2.- (Peptide Synthases)
EC 6.3.2.- (non-ribosomal peptide synthase)
0 (Peptides)

Date Created: 20241109 Date Completed: 20241109 Latest Revision: 20241116

20241116

PMC11546977

10.3390/ijms252111774

39519324