Blin K, Wolf T, Chevrette MG et al (2017) antiSMASH
4.0—improvements in chemistry prediction and
gene cluster boundary identification. Nucleic
Acids Res 45:W36–W41. https://doi.org/10.1093/
nar/gkx319
Blunt JW, Carroll AR, Copp BR et al (2018) Marine
natural products. Nat Prod Rep 35:8–53. https://
doi.org/10.1039/C7NP00052A
Bok JW, Keller NP (2004) LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot Cell
3:527–535.
https://doi.org/10.1128/EC.3.2.527535.2004
Bok JW, Hoffmeister D, Maggio-Hall LA et al (2006a)
Genomic mining for Aspergillus natural products.
Chem Biol 13:31–37. https://doi.org/10.1016/j.
chembiol.2005.10.008
Bok JW, Noordermeer D, Kale SP, Keller NP (2006b)
Secondary metabolic gene cluster silencing in
Aspergillus nidulans. Mol Microbiol 61:1636–1645.
https://doi.org/10.1111/j.1365-2958.2006.05330.x
Bok JW, Ye R, Clevenger KD et al (2015) Fungal artificial chromosomes for mining of the fungal secondary metabolome. BMC Genomics 16:343. https://
doi.org/10.1186/s12864-015-1561-x
Bouhired S, Weber M, Kempf-Sontag A et al (2007)
Accurate prediction of the Aspergillus nidulans
terrequinone gene cluster boundaries using the
transcriptional regulator LaeA. Fungal Genet
Biol
44:1134–1145.
https://doi.org/10.1016/j.
fgb.2006.12.010
Boya CAP, Ferna ´ndez-Marı ´n H, Mejı ´a LC et al (2017)
Imaging mass spectrometry and MS/MS molecular
networking reveals chemical interactions among
cuticular bacteria and pathogenic fungi associated
with fungus-growing ants. Sci Rep 7:5604. https://
doi.org/10.1038/s41598-017-05515-6
Bracarense AAP, Takahashi JA (2014) Modulation of
antimicrobial metabolites production by the
fungus Aspergillus parasiticus. Braz J Microbiol
45:313–321.
https://doi.org/10.1590/S151783822014000100045
Brakhage AA (2013) Regulation of fungal secondary
metabolism. Nat Rev Microbiol 11:21–32. https://
doi.org/10.1038/nrmicro2916
Brakhage AA, Schroeckh V (2011) Fungal secondary
metabolites—strategies to activate silent gene
clusters. Fungal Genet Biol 48:15–22. https://doi.
org/10.1016/j.fgb.2010.04.004
Bromann K, Toivari M, Viljanen K et al (2012) Identification and characterization of a novel diterpene
gene cluster in Aspergillus nidulans. PLoS One 7:
e35450.
https://doi.org/10.1371/journal.
pone.0035450
Brown DW, Proctor RH (2016) Insights into natural
products biosynthesis from analysis of 490
polyketide synthases from Fusarium. Fungal
Genet Biol 89:37–51. https://doi.org/10.1016/j.
fgb.2016.01.008
Bumpus SB, Evans BS, Thomas PM et al (2009) A proteomics approach to discovering natural products
and their biosynthetic pathways. Nat Biotechnol
27:951–956. https://doi.org/10.1038/nbt.1565
Cacho RA, Jiang W, Chooi YH et al (2012) Identification and characterization of the echinocandin B
biosynthetic gene cluster from Emericella rugulosa
NRRL 11440. J Am Chem Soc 134:16781–16790.
https://doi.org/10.1021/ja307220z
Cacho RA, Tang Y, Chooi YH (2015) Next-generation
sequencing approach for connecting secondary
metabolites to biosynthetic gene clusters in fungi.
Front Microbiol 5:774. https://doi.org/10.3389/
fmicb.2014.00774
Calvo AM, Wilson RA, Bok JW, Keller NP (2002) Relationship between secondary metabolism and fungal
development. Microbiol Mol Biol Rev 66:447–459.
https://doi.org/10.1128/MMBR.66.3.447-459.2002
Carberry S, Molloy E, Hammel S et al (2012) Gliotoxin
effects on fungal growth: mechanisms and exploitation. Fungal Genet Biol 49:302–312. https://doi.
org/10.1016/j.fgb.2012.02.003
Cha ´vez R, Fierro F, Garcı ´a-Rico RO, Vaca I (2015)
Filamentous fungi from extreme environments as
a promising source of novel bioactive secondary
metabolites. Front Microbiol 6:903. https://doi.
org/10.3389/fmicb.2015.00903
Chiang Y-M, Szewczyk E, Davidson AD et al (2009) A
gene cluster containing two fungal polyketide
synthases encodes the biosynthetic pathway for a
polyketide, asperfuranone, in Aspergillus nidulans. J Am Chem Soc 131:2965–2970. https://doi.
org/10.1021/ja8088185
Chooi YH, Cacho R, Tang Y (2010) Identification of
the viridicatumtoxin and griseofulvin gene clusters from Penicillium aethiopicum. Chem Biol
17:483–494.
https://doi.org/10.1016/j.chembiol.2010.03.015
Cooper MA, Shlaes D (2011) Fix the antibiotics pipeline. Nature 472:32–32. https://doi.org/10.1038/
472032a
Covington BC, McLean JA, Bachmann BO (2017) Comparative mass spectrometry-based metabolomics
strategies for the investigation of microbial secondary metabolites. Nat Prod Rep 34:6–24.
https://doi.org/10.1039/C6NP00048G
Cox DG, Oh J, Keasling A et al (2014) The utility of
metabolomics in natural product and biomarker
characterization. Biochim Biophys Acta Gen Subj
1840:3460–3474.
https://doi.org/10.1016/j.bbagen.2014.08.007
Cueto M, Jensen PR, Kauffman C et al (2001) Pestalone,
a new antibiotic produced by a marine fungus in
response to bacterial challenge. J Nat Prod
64:1444–1446
Currie CR (2001) A community of ants, fungi, and
bacteria: a multilateral approach to studying symbiosis. Annu Rev Microbiol 55:357–380. https://
doi.org/10.1146/annurev.micro.55.1.357
288
M. Flak et al.
4.0—improvements in chemistry prediction and
gene cluster boundary identification. Nucleic
Acids Res 45:W36–W41. https://doi.org/10.1093/
nar/gkx319
Blunt JW, Carroll AR, Copp BR et al (2018) Marine
natural products. Nat Prod Rep 35:8–53. https://
doi.org/10.1039/C7NP00052A
Bok JW, Keller NP (2004) LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot Cell
3:527–535.
https://doi.org/10.1128/EC.3.2.527535.2004
Bok JW, Hoffmeister D, Maggio-Hall LA et al (2006a)
Genomic mining for Aspergillus natural products.
Chem Biol 13:31–37. https://doi.org/10.1016/j.
chembiol.2005.10.008
Bok JW, Noordermeer D, Kale SP, Keller NP (2006b)
Secondary metabolic gene cluster silencing in
Aspergillus nidulans. Mol Microbiol 61:1636–1645.
https://doi.org/10.1111/j.1365-2958.2006.05330.x
Bok JW, Ye R, Clevenger KD et al (2015) Fungal artificial chromosomes for mining of the fungal secondary metabolome. BMC Genomics 16:343. https://
doi.org/10.1186/s12864-015-1561-x
Bouhired S, Weber M, Kempf-Sontag A et al (2007)
Accurate prediction of the Aspergillus nidulans
terrequinone gene cluster boundaries using the
transcriptional regulator LaeA. Fungal Genet
Biol
44:1134–1145.
https://doi.org/10.1016/j.
fgb.2006.12.010
Boya CAP, Ferna ´ndez-Marı ´n H, Mejı ´a LC et al (2017)
Imaging mass spectrometry and MS/MS molecular
networking reveals chemical interactions among
cuticular bacteria and pathogenic fungi associated
with fungus-growing ants. Sci Rep 7:5604. https://
doi.org/10.1038/s41598-017-05515-6
Bracarense AAP, Takahashi JA (2014) Modulation of
antimicrobial metabolites production by the
fungus Aspergillus parasiticus. Braz J Microbiol
45:313–321.
https://doi.org/10.1590/S151783822014000100045
Brakhage AA (2013) Regulation of fungal secondary
metabolism. Nat Rev Microbiol 11:21–32. https://
doi.org/10.1038/nrmicro2916
Brakhage AA, Schroeckh V (2011) Fungal secondary
metabolites—strategies to activate silent gene
clusters. Fungal Genet Biol 48:15–22. https://doi.
org/10.1016/j.fgb.2010.04.004
Bromann K, Toivari M, Viljanen K et al (2012) Identification and characterization of a novel diterpene
gene cluster in Aspergillus nidulans. PLoS One 7:
e35450.
https://doi.org/10.1371/journal.
pone.0035450
Brown DW, Proctor RH (2016) Insights into natural
products biosynthesis from analysis of 490
polyketide synthases from Fusarium. Fungal
Genet Biol 89:37–51. https://doi.org/10.1016/j.
fgb.2016.01.008
Bumpus SB, Evans BS, Thomas PM et al (2009) A proteomics approach to discovering natural products
and their biosynthetic pathways. Nat Biotechnol
27:951–956. https://doi.org/10.1038/nbt.1565
Cacho RA, Jiang W, Chooi YH et al (2012) Identification and characterization of the echinocandin B
biosynthetic gene cluster from Emericella rugulosa
NRRL 11440. J Am Chem Soc 134:16781–16790.
https://doi.org/10.1021/ja307220z
Cacho RA, Tang Y, Chooi YH (2015) Next-generation
sequencing approach for connecting secondary
metabolites to biosynthetic gene clusters in fungi.
Front Microbiol 5:774. https://doi.org/10.3389/
fmicb.2014.00774
Calvo AM, Wilson RA, Bok JW, Keller NP (2002) Relationship between secondary metabolism and fungal
development. Microbiol Mol Biol Rev 66:447–459.
https://doi.org/10.1128/MMBR.66.3.447-459.2002
Carberry S, Molloy E, Hammel S et al (2012) Gliotoxin
effects on fungal growth: mechanisms and exploitation. Fungal Genet Biol 49:302–312. https://doi.
org/10.1016/j.fgb.2012.02.003
Cha ´vez R, Fierro F, Garcı ´a-Rico RO, Vaca I (2015)
Filamentous fungi from extreme environments as
a promising source of novel bioactive secondary
metabolites. Front Microbiol 6:903. https://doi.
org/10.3389/fmicb.2015.00903
Chiang Y-M, Szewczyk E, Davidson AD et al (2009) A
gene cluster containing two fungal polyketide
synthases encodes the biosynthetic pathway for a
polyketide, asperfuranone, in Aspergillus nidulans. J Am Chem Soc 131:2965–2970. https://doi.
org/10.1021/ja8088185
Chooi YH, Cacho R, Tang Y (2010) Identification of
the viridicatumtoxin and griseofulvin gene clusters from Penicillium aethiopicum. Chem Biol
17:483–494.
https://doi.org/10.1016/j.chembiol.2010.03.015
Cooper MA, Shlaes D (2011) Fix the antibiotics pipeline. Nature 472:32–32. https://doi.org/10.1038/
472032a
Covington BC, McLean JA, Bachmann BO (2017) Comparative mass spectrometry-based metabolomics
strategies for the investigation of microbial secondary metabolites. Nat Prod Rep 34:6–24.
https://doi.org/10.1039/C6NP00048G
Cox DG, Oh J, Keasling A et al (2014) The utility of
metabolomics in natural product and biomarker
characterization. Biochim Biophys Acta Gen Subj
1840:3460–3474.
https://doi.org/10.1016/j.bbagen.2014.08.007
Cueto M, Jensen PR, Kauffman C et al (2001) Pestalone,
a new antibiotic produced by a marine fungus in
response to bacterial challenge. J Nat Prod
64:1444–1446
Currie CR (2001) A community of ants, fungi, and
bacteria: a multilateral approach to studying symbiosis. Annu Rev Microbiol 55:357–380. https://
doi.org/10.1146/annurev.micro.55.1.357
288
M. Flak et al.