Basidiomycete non-reducing polyketide synthases function independently of SAT domains.
Biosynthesis
Enzyme engineering
Orsellinic acid
Polyketide synthase
SAT domain
Journal
Fungal biology and biotechnology
ISSN: 2054-3085
Titre abrégé: Fungal Biol Biotechnol
Pays: England
ID NLM: 101655873
Informations de publication
Date de publication:
04 Aug 2023
04 Aug 2023
Historique:
received:
22
05
2023
accepted:
16
07
2023
medline:
5
8
2023
pubmed:
5
8
2023
entrez:
4
8
2023
Statut:
epublish
Résumé
Non-reducing polyketide synthases (NR-PKSs) account for a major share of natural product diversity produced by both Asco- and Basidiomycota. The present evolutionary diversification into eleven clades further underscores the relevance of these multi-domain enzymes. Following current knowledge, NR-PKSs initiate polyketide assembly by an N-terminal starter unit:acyl transferase (SAT) domain that catalyzes the transfer of an acetyl starter from the acetyl-CoA thioester onto the acyl carrier protein (ACP). A comprehensive phylogenetic analysis of NR-PKSs established a twelfth clade from which three representatives, enzymes CrPKS1-3 of the webcap mushroom Cortinarius rufoolivaceus, were biochemically characterized. These basidiomycete synthases lack a SAT domain yet are fully functional hepta- and octaketide synthases in vivo. Three members of the other clade of basidiomycete NR-PKSs (clade VIII) were produced as SAT-domainless versions and analyzed in vivo and in vitro. They retained full activity, thus corroborating the notion that the SAT domain is dispensable for many basidiomycete NR-PKSs. For comparison, the ascomycete octaketide synthase atrochrysone carboxylic acid synthase (ACAS) was produced as a SAT-domainless enzyme as well, but turned out completely inactive. However, a literature survey revealed that some NR-PKSs of ascomycetes carry mutations within the catalytic motif of the SAT domain. In these cases, the role of the domain and the origin of the formal acetate unit remains open. The role of SAT domains differs between asco- and basidiomycete NR-PKSs. For the latter, it is not part of the minimal set of NR-PKS domains and not required for function. This knowledge may help engineer compact NR-PKSs for more resource-efficient routes. From the genomic standpoint, seemingly incomplete or corrupted genes encoding SAT-domainless NR-PKSs should not automatically be dismissed as non-functional pseudogenes, but considered during genome analysis to decipher the potential arsenal of natural products of a given fungus.
Sections du résumé
BACKGROUND
BACKGROUND
Non-reducing polyketide synthases (NR-PKSs) account for a major share of natural product diversity produced by both Asco- and Basidiomycota. The present evolutionary diversification into eleven clades further underscores the relevance of these multi-domain enzymes. Following current knowledge, NR-PKSs initiate polyketide assembly by an N-terminal starter unit:acyl transferase (SAT) domain that catalyzes the transfer of an acetyl starter from the acetyl-CoA thioester onto the acyl carrier protein (ACP).
RESULTS
RESULTS
A comprehensive phylogenetic analysis of NR-PKSs established a twelfth clade from which three representatives, enzymes CrPKS1-3 of the webcap mushroom Cortinarius rufoolivaceus, were biochemically characterized. These basidiomycete synthases lack a SAT domain yet are fully functional hepta- and octaketide synthases in vivo. Three members of the other clade of basidiomycete NR-PKSs (clade VIII) were produced as SAT-domainless versions and analyzed in vivo and in vitro. They retained full activity, thus corroborating the notion that the SAT domain is dispensable for many basidiomycete NR-PKSs. For comparison, the ascomycete octaketide synthase atrochrysone carboxylic acid synthase (ACAS) was produced as a SAT-domainless enzyme as well, but turned out completely inactive. However, a literature survey revealed that some NR-PKSs of ascomycetes carry mutations within the catalytic motif of the SAT domain. In these cases, the role of the domain and the origin of the formal acetate unit remains open.
CONCLUSIONS
CONCLUSIONS
The role of SAT domains differs between asco- and basidiomycete NR-PKSs. For the latter, it is not part of the minimal set of NR-PKS domains and not required for function. This knowledge may help engineer compact NR-PKSs for more resource-efficient routes. From the genomic standpoint, seemingly incomplete or corrupted genes encoding SAT-domainless NR-PKSs should not automatically be dismissed as non-functional pseudogenes, but considered during genome analysis to decipher the potential arsenal of natural products of a given fungus.
Identifiants
pubmed: 37542286
doi: 10.1186/s40694-023-00164-z
pii: 10.1186/s40694-023-00164-z
pmc: PMC10401856
doi:
Types de publication
Journal Article
Langues
eng
Pagination
17Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : HO2515/8-1
Informations de copyright
© 2023. The Author(s).
Références
Nat Prod Rep. 2007 Feb;24(1):162-90
pubmed: 17268612
Proc Natl Acad Sci U S A. 2016 Jun 21;113(25):6851-6
pubmed: 27274078
Nat Prod Rep. 2007 Apr;24(2):393-416
pubmed: 17390002
Org Biomol Chem. 2007 Jul 7;5(13):2010-26
pubmed: 17581644
mBio. 2021 Jun 29;12(3):e0111121
pubmed: 34154413
Sci Rep. 2015 May 21;5:10463
pubmed: 25995122
Mol Biol Evol. 2018 Jun 1;35(6):1547-1549
pubmed: 29722887
Nat Prod Rep. 2021 Apr 28;38(4):702-722
pubmed: 33404035
Chem Commun (Camb). 2016 May 21;52(41):6777-80
pubmed: 27056201
Nat Prod Rep. 2023 Jan 25;40(1):9-27
pubmed: 35543313
FEBS J. 2007 Jan;274(2):406-17
pubmed: 17229146
Chembiochem. 2012 Apr 16;13(6):846-54
pubmed: 22447505
Microbiol Spectr. 2022 Oct 26;10(5):e0106522
pubmed: 36094086
Nat Prod Rep. 2007 Oct;24(5):1041-72
pubmed: 17898897
Angew Chem Int Ed Engl. 2023 Feb 1;62(6):e202214379
pubmed: 36484777
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15670-5
pubmed: 14676319
Fungal Biol Biotechnol. 2022 Apr 27;9(1):8
pubmed: 35477441
Chembiochem. 2012 Sep 3;13(13):1880-4
pubmed: 22807303
Chem Biol. 2008 Dec 22;15(12):1328-38
pubmed: 19101477
Appl Environ Microbiol. 2010 Apr;76(8):2487-99
pubmed: 20154113
Fortschr Chem Org Naturst. 1987;51:1-317
pubmed: 3315906
Angew Chem Int Ed Engl. 2016 Jan 11;55(2):664-8
pubmed: 26783060
J Biol Chem. 2010 Jul 23;285(30):22764-73
pubmed: 20479000
J Bacteriol. 1995 Aug;177(16):4792-800
pubmed: 7642507
Nature. 1999 Sep 30;401(6752):502-5
pubmed: 10519556
Nat Prod Rep. 2001 Aug;18(4):380-416
pubmed: 11548049
Commun Biol. 2022 May 26;5(1):508
pubmed: 35618872
Front Microbiol. 2015 Mar 16;6:184
pubmed: 25852654
J Am Chem Soc. 2012 Apr 18;134(15):6865-77
pubmed: 22452347
Appl Environ Microbiol. 2010 Apr;76(7):2067-74
pubmed: 20139316
Nat Protoc. 2007;2(6):1528-35
pubmed: 17571060
Chem Sci. 2014 Feb 23;5(2):523-527
pubmed: 25580210
FEMS Microbiol Ecol. 2015 Nov;91(11):
pubmed: 26449385
J Am Chem Soc. 2009 Mar 4;131(8):2965-70
pubmed: 19199437
Fungal Genet Biol. 2017 Jan;98:12-19
pubmed: 27903443
Org Lett. 2014 Mar 21;16(6):1676-9
pubmed: 24593241
mBio. 2022 Jun 28;13(3):e0022322
pubmed: 35616333
J Am Chem Soc. 2012 May 16;134(19):8212-21
pubmed: 22510154
Appl Microbiol Biotechnol. 2017 Jun;101(11):4701-4711
pubmed: 28255687
J Nat Prod. 2016 Jun 24;79(6):1485-91
pubmed: 27227778
Sci Rep. 2018 Jul 2;8(1):9982
pubmed: 29967427
J Am Chem Soc. 2010 Apr 7;132(13):4530-1
pubmed: 20222707
Angew Chem Int Ed Engl. 2021 May 10;60(20):11423-11429
pubmed: 33661567
Curr Opin Chem Biol. 2021 Feb;60:47-54
pubmed: 32853968
Org Biomol Chem. 2010 Aug 7;8(15):3543-51
pubmed: 20532365
Toxins (Basel). 2015 Sep 10;7(9):3572-607
pubmed: 26378577
J Am Chem Soc. 2015 Aug 12;137(31):9885-93
pubmed: 26172141
J Am Chem Soc. 2007 Sep 5;129(35):10642-3
pubmed: 17696354
Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1418-22
pubmed: 8643646
Nat Commun. 2018 Sep 26;9(1):3940
pubmed: 30258052
Angew Chem Int Ed Engl. 2009;48(26):4688-716
pubmed: 19514004
Genome Res. 2017 May;27(5):722-736
pubmed: 28298431
Genomics Proteomics Bioinformatics. 2016 Oct;14(5):265-279
pubmed: 27646134
Nat Biotechnol. 2018 Oct 22;:
pubmed: 30346939
Front Plant Sci. 2016 Sep 27;7:1452
pubmed: 27729920
J Biol Chem. 2003 Nov 7;278(45):44780-90
pubmed: 12941968
Nat Prod Rep. 2023 Jan 25;40(1):174-201
pubmed: 36222427
Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6249-54
pubmed: 18427109
Chembiochem. 2008 May 5;9(7):1019-23
pubmed: 18338425
Nat Prod Rep. 2012 Oct;29(10):1050-73
pubmed: 22858605
Chembiochem. 2020 Feb 17;21(4):564-571
pubmed: 31430416
Nat Rev Microbiol. 2010 Dec;8(12):879-89
pubmed: 21079635
Mol Gen Genet. 1996 Nov 27;253(1-2):1-10
pubmed: 9003280
Eur J Biochem. 1990 Sep 11;192(2):487-98
pubmed: 2209605
Nucleic Acids Res. 2016 Jul 8;44(W1):W232-5
pubmed: 27084950
Mol Biol Evol. 2018 Feb 1;35(2):518-522
pubmed: 29077904
Nucleic Acids Res. 2021 Jan 8;49(D1):D412-D419
pubmed: 33125078
Chem Biol. 2013 Sep 19;20(9):1101-6
pubmed: 23993460
BMC Bioinformatics. 2004 Aug 19;5:113
pubmed: 15318951
Fungal Genet Biol. 2012 Dec;49(12):996-1003
pubmed: 23078836
Nat Genet. 2015 Apr;47(4):410-5
pubmed: 25706625
Org Lett. 2014 Dec 19;16(24):6390-3
pubmed: 25494235
Angew Chem Int Ed Engl. 2022 Jun 13;61(24):e202116142
pubmed: 35218274
Mycopathologia. 2006 May;161(5):283-94
pubmed: 16649078
Bioorg Chem. 2008 Feb;36(1):16-22
pubmed: 18215412
Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
pubmed: 9254694
Chem Biol. 2009 Jun 26;16(6):613-23
pubmed: 19549600
J Biol Chem. 2010 Dec 31;285(53):41412-21
pubmed: 20961859
Cell Chem Biol. 2019 Feb 21;26(2):223-234.e6
pubmed: 30527997
Nat Prod Rep. 2010 Feb;27(2):255-78
pubmed: 20111804
Chembiochem. 2020 May 15;21(10):1423-1427
pubmed: 32159919
Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16728-33
pubmed: 17071746
Nat Prod Rep. 2021 May 1;38(5):1011-1043
pubmed: 33196733
Angew Chem Int Ed Engl. 2013 Feb 4;52(6):1718-21
pubmed: 23283670
Nat Methods. 2017 Jun;14(6):587-589
pubmed: 28481363
Chem Biol. 2011 Feb 25;18(2):198-209
pubmed: 21236704
Fungal Biol Biotechnol. 2017 Dec 19;4:13
pubmed: 29270299
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W309-12
pubmed: 15215400
Nature. 2009 Oct 22;461(7267):1139-43
pubmed: 19847268
Microb Biotechnol. 2017 Jul;10(4):958-968
pubmed: 28618182
Appl Environ Microbiol. 2004 Mar;70(3):1253-62
pubmed: 15006741
Chembiochem. 2023 Feb 1;24(3):e202200649
pubmed: 36507600
Appl Environ Microbiol. 2008 Aug;74(16):5121-9
pubmed: 18567690
J Am Chem Soc. 2012 Oct 31;134(43):17900-3
pubmed: 23072467