challenges and perspectives. Int J Mol Sci 17:1275.
https://doi.org/10.3390/ijms17081275
Wang G, Liu Z, Lin R et al (2016b) Biosynthesis of
antibiotic leucinostatins in bio-control fungus
Purpureocillium lilacinum and their inhibition on
Phytophthora revealed by genome mining. PLoS
Pathog 12:e1005685. https://doi.org/10.1371/journal.ppat.1005685
Wang M, Carver JJ, Phelan VV et al (2016c) Sharing and
community curation of mass spectrometry data
with Global Natural Products Social Molecular
Networking. Nat Biotechnol 34:828–837. https://
doi.org/10.1038/nbt.3597
Wanka F, Cairns T, Boecker S et al (2016) Tet-on, or
Tet-off, that is the question: advanced conditional
gene expression in Aspergillus. Fungal Genet Biol
89:72–83. https://doi.org/10.1016/j.fgb.2015.11.003
Waring RB, May GS, Morris NR (1989) Characterization of an inducible expression system in Aspergillus nidulans using alcA and tubulin coding genes.
Gene 79:119–130. https://doi.org/10.1016/03781119(89)90097-8
Weber T (2014) In silico tools for the analysis of antibiotic biosynthetic pathways. Int J Med Microbiol
304:230–235.
https://doi.org/10.1016/j.
ijmm.2014.02.001
Weber J, Valiante V, Nødvig CS et al (2017) Functional
reconstitution of a fungal natural product gene
cluster by advanced genome editing. ACS Synth
Biol 6:62–68. https://doi.org/10.1021/acssynbio.6b00203
Weissman KJ (2016) Genetic engineering of modular
PKSs: from combinatorial biosynthesis to synthetic biology. Nat Prod Rep 33:203–230. https://
doi.org/10.1039/C5NP00109A
West RR, van Ness J, Varming AM et al (1996) ZG1494a, a novel platelet-activating factor acetyltransferase inhibitor from Penicilium rubrum, isolation, structure elucidation and biological
activity. J Antibiot (Tokyo) 49:967–973. https://
doi.org/10.7164/antibiotics.49.967
WHO (2017) 20th edition WHO model list of essential
medicines (March 2017)
Wiemann P, Guo CJ, Palmer JM et al (2013a) Prototype
of an intertwined secondary-metabolite supercluster. Proc Natl Acad Sci U S A 110:17065–17070.
https://doi.org/10.1073/pnas.1313258110
Wiemann P, Sieber CMK, von Bargen KW et al (2013b)
Deciphering the cryptic genome: genome-wide
analyses of the rice pathogen Fusarium fujikuroi
reveal complex regulation of secondary metabolism and novel metabolites. PLoS Pathog 9:
e1003475.
https://doi.org/10.1371/journal.
ppat.1003475
Wiemann P, Soukup AA, Folz JS et al (2018) CoIN: coinducible nitrate expression system for secondary
metabolites in Aspergillus nidulans. Fungal Biol
Biotechnol 5:6. https://doi.org/10.1186/s40694018-0049-2
Wolfender JL, Marti G, Thomas A, Bertrand S (2015)
Current approaches and challenges for the metabolite profiling of complex natural extracts. J Chromatogr A 1382:136–164. https://doi.org/10.1016/j.
chroma.2014.10.091
Wunsch C, Mundt K, Li SM (2015) Targeted production
of secondary metabolites by coexpression of nonribosomal peptide synthetase and prenyltransferase genes in Aspergillus. Appl Microbiol Biotechnol 99:4213–4223. https://doi.org/10.1007/s00253015-6490-8
Xu W, Cai X, Jung ME, Tang Y (2010) Analysis of intact
and dissected fungal polyketide synthasenonribosomal peptide synthetase in vitro and in
Saccharomyces cerevisiae. J Am Chem Soc
132:13604–13607. https://doi.org/10.1021/ja107084d
Yeger-Lotem E, Riva L, Su LJ et al (2009) Bridging highthroughput genetic and transcriptional data
reveals cellular responses to alpha-synuclein toxicity. Nat Genet 41:316–323. https://doi.org/
10.1038/ng.337
Yin W, Keller NP (2011) Transcriptional regulatory
elements in fungal secondary metabolism. J Microbiol 49:329–339. https://doi.org/10.1007/s12275011-1009-1
Zabala AO, Xu W, Chooi Y-H, Tang Y (2012) Characterization of a silent azaphilone gene cluster
from Aspergillus niger ATCC 1015 reveals a
hydroxylation-mediated pyran-ring formation.
Chem Biol 19:1049–1059. https://doi.org/10.1016/
j.chembiol.2012.07.004
Zadra I, Abt B, Parson W, Haas H (2000) xylP
promoter-based expression system and its use for
antisense downregulation of the Penicillium chrysogenum nitrogen regulator NRE. Appl Environ
Microbiol 66:4810–4816. https://doi.org/10.1128/
AEM.66.11.4810-4816.2000
Zhang XW, Jia LJ, Zhang Y et al (2012) In planta stagespecific fungal gene profiling elucidates the molecular strategies of Fusarium graminearum growing
inside wheat coleoptiles. Plant Cell 24:5159–5176.
https://doi.org/10.1105/tpc.112.105957
Zhang L, Niaz S, Khan D et al (2017) Induction of
diverse bioactive secondary metabolites from the
mangrove endophytic fungus Trichoderma sp.
(strain 307) by co-cultivation with Acinetobacter
johnsonii (strain B2). Mar Drugs 15:35. https://doi.
org/10.3390/md15020035
Zhang T, Wan J, Zhan Z et al (2018) Activation of an
unconventional meroterpenoid gene cluster in
Neosartorya glabra leads to the production of
new berkeleyacetals. Acta Pharm Sin B 8:478–487.
https://doi.org/10.1016/j.apsb.2017.12.005
Zhao Y, Liu D, Proksch P et al (2018) Truncateols
O-V, further isoprenylated cyclohexanols from
the sponge-associated fungus Truncatella angustata with antiviral activities. Phytochemistry
155:61–68.
https://doi.org/10.1016/j.phytochem.2018.07.017
294
M. Flak et al.
https://doi.org/10.3390/ijms17081275
Wang G, Liu Z, Lin R et al (2016b) Biosynthesis of
antibiotic leucinostatins in bio-control fungus
Purpureocillium lilacinum and their inhibition on
Phytophthora revealed by genome mining. PLoS
Pathog 12:e1005685. https://doi.org/10.1371/journal.ppat.1005685
Wang M, Carver JJ, Phelan VV et al (2016c) Sharing and
community curation of mass spectrometry data
with Global Natural Products Social Molecular
Networking. Nat Biotechnol 34:828–837. https://
doi.org/10.1038/nbt.3597
Wanka F, Cairns T, Boecker S et al (2016) Tet-on, or
Tet-off, that is the question: advanced conditional
gene expression in Aspergillus. Fungal Genet Biol
89:72–83. https://doi.org/10.1016/j.fgb.2015.11.003
Waring RB, May GS, Morris NR (1989) Characterization of an inducible expression system in Aspergillus nidulans using alcA and tubulin coding genes.
Gene 79:119–130. https://doi.org/10.1016/03781119(89)90097-8
Weber T (2014) In silico tools for the analysis of antibiotic biosynthetic pathways. Int J Med Microbiol
304:230–235.
https://doi.org/10.1016/j.
ijmm.2014.02.001
Weber J, Valiante V, Nødvig CS et al (2017) Functional
reconstitution of a fungal natural product gene
cluster by advanced genome editing. ACS Synth
Biol 6:62–68. https://doi.org/10.1021/acssynbio.6b00203
Weissman KJ (2016) Genetic engineering of modular
PKSs: from combinatorial biosynthesis to synthetic biology. Nat Prod Rep 33:203–230. https://
doi.org/10.1039/C5NP00109A
West RR, van Ness J, Varming AM et al (1996) ZG1494a, a novel platelet-activating factor acetyltransferase inhibitor from Penicilium rubrum, isolation, structure elucidation and biological
activity. J Antibiot (Tokyo) 49:967–973. https://
doi.org/10.7164/antibiotics.49.967
WHO (2017) 20th edition WHO model list of essential
medicines (March 2017)
Wiemann P, Guo CJ, Palmer JM et al (2013a) Prototype
of an intertwined secondary-metabolite supercluster. Proc Natl Acad Sci U S A 110:17065–17070.
https://doi.org/10.1073/pnas.1313258110
Wiemann P, Sieber CMK, von Bargen KW et al (2013b)
Deciphering the cryptic genome: genome-wide
analyses of the rice pathogen Fusarium fujikuroi
reveal complex regulation of secondary metabolism and novel metabolites. PLoS Pathog 9:
e1003475.
https://doi.org/10.1371/journal.
ppat.1003475
Wiemann P, Soukup AA, Folz JS et al (2018) CoIN: coinducible nitrate expression system for secondary
metabolites in Aspergillus nidulans. Fungal Biol
Biotechnol 5:6. https://doi.org/10.1186/s40694018-0049-2
Wolfender JL, Marti G, Thomas A, Bertrand S (2015)
Current approaches and challenges for the metabolite profiling of complex natural extracts. J Chromatogr A 1382:136–164. https://doi.org/10.1016/j.
chroma.2014.10.091
Wunsch C, Mundt K, Li SM (2015) Targeted production
of secondary metabolites by coexpression of nonribosomal peptide synthetase and prenyltransferase genes in Aspergillus. Appl Microbiol Biotechnol 99:4213–4223. https://doi.org/10.1007/s00253015-6490-8
Xu W, Cai X, Jung ME, Tang Y (2010) Analysis of intact
and dissected fungal polyketide synthasenonribosomal peptide synthetase in vitro and in
Saccharomyces cerevisiae. J Am Chem Soc
132:13604–13607. https://doi.org/10.1021/ja107084d
Yeger-Lotem E, Riva L, Su LJ et al (2009) Bridging highthroughput genetic and transcriptional data
reveals cellular responses to alpha-synuclein toxicity. Nat Genet 41:316–323. https://doi.org/
10.1038/ng.337
Yin W, Keller NP (2011) Transcriptional regulatory
elements in fungal secondary metabolism. J Microbiol 49:329–339. https://doi.org/10.1007/s12275011-1009-1
Zabala AO, Xu W, Chooi Y-H, Tang Y (2012) Characterization of a silent azaphilone gene cluster
from Aspergillus niger ATCC 1015 reveals a
hydroxylation-mediated pyran-ring formation.
Chem Biol 19:1049–1059. https://doi.org/10.1016/
j.chembiol.2012.07.004
Zadra I, Abt B, Parson W, Haas H (2000) xylP
promoter-based expression system and its use for
antisense downregulation of the Penicillium chrysogenum nitrogen regulator NRE. Appl Environ
Microbiol 66:4810–4816. https://doi.org/10.1128/
AEM.66.11.4810-4816.2000
Zhang XW, Jia LJ, Zhang Y et al (2012) In planta stagespecific fungal gene profiling elucidates the molecular strategies of Fusarium graminearum growing
inside wheat coleoptiles. Plant Cell 24:5159–5176.
https://doi.org/10.1105/tpc.112.105957
Zhang L, Niaz S, Khan D et al (2017) Induction of
diverse bioactive secondary metabolites from the
mangrove endophytic fungus Trichoderma sp.
(strain 307) by co-cultivation with Acinetobacter
johnsonii (strain B2). Mar Drugs 15:35. https://doi.
org/10.3390/md15020035
Zhang T, Wan J, Zhan Z et al (2018) Activation of an
unconventional meroterpenoid gene cluster in
Neosartorya glabra leads to the production of
new berkeleyacetals. Acta Pharm Sin B 8:478–487.
https://doi.org/10.1016/j.apsb.2017.12.005
Zhao Y, Liu D, Proksch P et al (2018) Truncateols
O-V, further isoprenylated cyclohexanols from
the sponge-associated fungus Truncatella angustata with antiviral activities. Phytochemistry
155:61–68.
https://doi.org/10.1016/j.phytochem.2018.07.017
294
M. Flak et al.