Regulation of Secondary Metabolism by the Velvet Complex Is Temperature-Responsive in Aspergillus.
Sensing and responding to environmental cues is critical to the lifestyle of filamentous fungi. How environmental variation influences fungi to produce a wide diversity of ecologically important secondary metabolites (SMs) is not well understood. To address this question, we first examined changes in global gene expression of the opportunistic human pathogen, Aspergillus fumigatus, after exposure to different temperature conditions. We found that 11 of the 37 SM gene clusters in A. fumigatus were expressed at higher levels at 30° than at 37°. We next investigated the role of the light-responsive Velvet complex in environment-dependent gene expression by examining temperature-dependent transcription profiles in the absence of two key members of the Velvet protein complex, VeA and LaeA We found that the 11 temperature-regulated SM gene clusters required VeA at 37° and LaeA at both 30 and 37° for wild-type levels of expression. Interestingly, four SM gene clusters were regulated by VeA at 37° but not at 30°, and two additional ones were regulated by VeA at both temperatures but were substantially less so at 30°, indicating that the role of VeA and, more generally of the Velvet complex, in the regulation of certain SM gene clusters is temperature-dependent. Our findings support the hypothesis that fungal secondary metabolism is regulated by an intertwined network of transcriptional regulators responsive to multiple environmental factors.
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee 37203.
Abigail L
0000-0002-9579-4178
AL
Lind
Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois 60115.
Timothy D
TD
Smith
Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois 60115.
Timothy
T
Saterlee
Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois 60115 amcalvo@niu.edu antonis.rokas@vanderbilt.edu.
Ana M
AM
Calvo
Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37232 amcalvo@niu.edu antonis.rokas@vanderbilt.edu.
Antonis
0000-0002-7248-6551
A
Rokas
D001230:Aspergillus / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005810:Multigene Family; D064210:Secondary Metabolism; D013696:Temperature
D005656:Fungal Proteins
Aspergillus fumigatus; gene cluster; gene regulation; temperature-dependent gene expression
PLoS Pathog. 2013;9(4):e1003289
23592999
Bioinformatics. 2015 Jan 15;31(2):166-9
25260700
Appl Environ Microbiol. 1998 Jun;64(6):2275-7
9603849
Mol Microbiol. 2016 Mar;99(5):909-24
26564476
Chem Biol. 2006 Jan;13(1):31-7
16426969
FEMS Microbiol Lett. 2011 Sep;322(2):145-9
21707733
Mol Microbiol. 2010 Aug;77(4):972-94
20572938
Biochemistry. 2010 Oct 5;49(39):8564-76
20804163
J Am Chem Soc. 2013 Mar 27;135(12):4616-9
23488861
PLoS One. 2013 Oct 07;8(10):e77147
24116213
PLoS Genet. 2015 Mar 18;11(3):e1005096
25786130
FEMS Microbiol Rev. 2012 Jan;36(1):1-24
21658084
Genome Biol. 2013 Apr 25;14(4):R36
23618408
Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):17065-70
24082142
Mycologia. 2007 Mar-Apr;99(2):232-9
17682776
Genome Res. 2003 Nov;13(11):2498-504
14597658
Med Mycol. 2009;47 Suppl 1:S88-96
19255906
BMC Microbiol. 2013 Apr 26;13:91
23617571
ACS Chem Biol. 2012 Mar 16;7(3):599-606
22234162
BMC Genomics. 2012 Feb 06;13:62
22309491
Fungal Genet Biol. 2012 Feb;49(2):141-51
22227160
Fungal Genet Biol. 2010 Dec;47(12):962-72
20816830
Nucleic Acids Res. 2010 Jan;38(Database issue):D420-7
19773420
Bioinformatics. 2014 Aug 1;30(15):2114-20
24695404
Nat Rev Microbiol. 2013 Jan;11(1):21-32
23178386
Elife. 2015 Jul 14;4:null
26173180
Chembiochem. 2013 May 27;14(8):938-42
23649940
Dev Cell. 2014 May 27;29(4):406-20
24871947
Fungal Genet Biol. 2008 Jul;45(7):1053-61
18457967
Nucleic Acids Res. 2012 Jan;40(Database issue):D653-9
22080559
Appl Microbiol Biotechnol. 2012 Jan;93(2):467-72
22094977
Microbes Infect. 2007 Jan;9(1):47-54
17196420
J Appl Microbiol. 2003;94(1):127-37
12492933
PLoS Genet. 2013;9(1):e1003193
23341778
Science. 2008 Jun 13;320(5882):1504-6
18556559
Mol Microbiol. 2015 Apr;96(1):148-62
25582336
Bioinformatics. 2005 Aug 15;21(16):3448-9
15972284
Chembiochem. 2006 Jul;7(7):1062-9
16755625
FEMS Microbiol Lett. 2005 Jul 15;248(2):241-8
15979823
Front Microbiol. 2015 Feb 16;6:62
25762985
Appl Environ Microbiol. 2012 Jun;78(12):4117-25
22492455
J Bacteriol. 1999 Oct;181(20):6469-77
10515939
Front Microbiol. 2015 Jan 20;6:1
25653648
Environ Microbiol. 2016 Jan;18(1):246-59
26242966
Mol Microbiol. 2005 Feb;55(4):1072-84
15686555
PLoS Pathog. 2007 Apr;3(4):e50
17432932
Nat Rev Microbiol. 2005 Dec;3(12):937-47
16322742
Mol Plant Microbe Interact. 1995 Jul-Aug;8(4):593-601
8589414
Eukaryot Cell. 2010 Aug;9(8):1236-50
20543063
Med Mycol. 2009;47 Suppl 1:S53-71
18763205
Mol Genet Genomics. 2009 Jan;281(1):35-42
18936976
EMBO J. 1995 Feb 15;14(4):779-90
7882981
Rev Iberoam Micol. 2010 Oct-Dec;27(4):155-82
20974273
Appl Microbiol Biotechnol. 2015 Dec;99(23):10151-61
26278536
Philos Trans R Soc Lond B Biol Sci. 2007 Jul 29;362(1483):1195-200
17360275
Biol Lett. 2007 Oct 22;3(5):523-5
17686752
Science. 1999 May 21;284(5418):1368-72
10334994
Clin Microbiol Rev. 2003 Jul;16(3):497-516
12857779
Chem Biol. 2008 Jun;15(6):527-32
18559263
Mycologia. 2012 Jul-Aug;104(4):804-12
22453123
Nucleic Acids Res. 2015 Jan;43(Database issue):D1049-56
25428369
Eukaryot Cell. 2012 Dec;11(12):1531-43
23087369
Fungal Genet Biol. 2014 Jan;62:78-84
24240057
J Am Chem Soc. 2013 Feb 13;135(6):2064-7
23360537
PLoS Genet. 2011 Dec;7(12):e1002374
22144905
Blood. 2005 Mar 15;105(6):2258-65
15546954
Nat Chem Biol. 2015 Sep;11(9):671-7
26284674
Med Mycol. 1998;36 Suppl 1:137-45
9988502
Curr Biol. 2008 Feb 26;18(4):255-9
18291652
Clin Microbiol Rev. 1999 Apr;12(2):310-50
10194462
Genome Biol. 2014;15(12):550
25516281