Netzker T, Flak M, Krespach MK et al (2018) Microbial
interactions trigger the production of antibiotics.
Curr Opin Microbiol 45:117–123. https://doi.org/
10.1016/j.mib.2018.04.002
Nichols D, Cahoon N, Trakhtenberg EM et al (2010)
Use of iChip for high-throughput in situ cultivation of ‘uncultivable’ microbial species. Appl Environ Microbiol 76:2445–2450. https://doi.org/
10.1128/AEM.01754-09
Nielsen ML, Isbrandt T, Petersen LM et al (2016) Linker
flexibility facilitates module exchange in fungal
hybrid PKS-NRPS engineering. PLoS One 11:
e0161199.
https://doi.org/10.1371/journal.
pone.0161199
Nielsen ML, Isbrandt T, Rasmussen KB et al (2017)
Genes linked to production of secondary metabolites in Talaromyces atroroseus revealed using
CRISPR-Cas9. PLoS One 12:e0169712. https://doi.
org/10.1371/journal.pone.0169712
Nødvig CS, Nielsen JB, Kogle ME, Mortensen UH
(2015) A CRISPR-Cas9 system for genetic engineering of filamentous fungi. PLoS One
10:0133085.
https://doi.org/10.1371/journal.
pone.0133085
Oakley CE, Ahuja M, Sun WW et al (2017) Discovery of
McrA, a master regulator of Aspergillus secondary
metabolism. Mol Microbiol 103:347–365. https://
doi.org/10.1111/mmi.13562
Okuda S, Yamada T, Hamajima M et al (2008) KEGG
Atlas mapping for global analysis of metabolic
pathways. Nucleic Acids Res 36:W423–W426.
https://doi.org/10.1093/nar/gkn282
Omura S, Ikeda H, Malpartida F et al (1986) Production
of new hybrid antibiotics, mederrhodins A and B,
by a genetically engineered strain. Antimicrob
Agents Chemother 29:13–19. https://doi.org/
10.1128/AAC.29.1.13
Owen JG, Calcott MJ, Robins KJ, Ackerley DF (2016)
Generating functional recombinant NRPS
enzymes in the laboratory setting via peptidyl carrier protein engineering. Cell Chem Biol 23:1395–
1406.
https://doi.org/10.1016/j.chembiol.2016.09.014
Owens RA, Hammel S, Sheridan KJ et al (2014) A
proteomic approach to investigating gene cluster
expression and secondary metabolite functionality
in Aspergillus fumigatus. PLoS One 9:e106942.
https://doi.org/10.1371/journal.pone.0106942
Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL
(2007) Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug
Discov 6:29–40. https://doi.org/10.1038/nrd2201
Pfannenstiel BT, Zhao X, Wortman J et al (2017) Revitalization of a forward genetic screen identifies
three new regulators of fungal secondary metabolism in the genus Aspergillus. MBio 8:e01246–
e01217. https://doi.org/10.1128/mBio.01246-17
Piechulla B, Degenhardt J (2014) The emerging importance of microbial volatile organic compounds.
Plant Cell Environ 37:811–812. https://doi.org/
10.1111/pce.12254
Robey MT, Ye R, Bok JW et al (2018) Identification of
the first diketomorpholine biosynthetic pathway
using FAC-MS technology. ACS Chem Biol
13:1142–1147. https://doi.org/10.1021/acschembio.8b00024
Robinson SL, Panaccione DG (2014) Heterologous
expression of lysergic acid and novel ergot alkaloids in Aspergillus fumigatus. Appl Environ
Microbiol 80:6465–6472. https://doi.org/10.1128/
AEM.02137-14
Rutledge PJ, Challis GL (2015) Discovery of microbial
natural products by activation of silent biosynthetic gene clusters. Nat Rev Microbiol 13:509–
523. https://doi.org/10.1038/nrmicro3496
Sakai K, Kinoshita H, Shimizu T, Nihira T (2008) Construction of a citrinin gene cluster expression system in heterologous Aspergillus oryzae. J Biosci
Bioeng 106:466–472. https://doi.org/10.1263/
jbb.106.466
Sanchez JF, Somoza AD, Keller NP, Wang CCC (2012)
Advances in Aspergillus secondary metabolite
research in the post-genomic era. Nat Prod Rep
29:351. https://doi.org/10.1039/c2np00084a
Schmidt K, Podmore I (2015) Current challenges in
volatile organic compounds analysis as potential
biomarkers of cancer. J Biomarkers 2015:1–16.
https://doi.org/10.1155/2015/981458
Schmidt-Dannert C (2015) NextGen microbial natural
products discovery. Microb Biotechnol 8:26–28.
https://doi.org/10.1111/1751-7915.12184
Schroeckh V, Scherlach K, Nu ¨tzmann HW et al (2009)
Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus
nidulans. Proc Natl Acad Sci U S A 106:14558–
14563. https://doi.org/10.1073/pnas.0901870106
Schuetze T, Meyer V (2017) Polycistronic gene expression in Aspergillus niger. Microb Cell Factories
16:162. https://doi.org/10.1186/s12934-017-0780-z
Schu ¨mann J, Hertweck C (2006) Advances in cloning,
functional analysis and heterologous expression of
fungal polyketide synthase genes. J Biotechnol
124:690–703.
https://doi.org/10.1016/j.jbiotec.2006.03.046
Schuster M, Schweizer G, Reissmann S, Kahmann R
(2016) Genome editing in Ustilago maydis using
the CRISPR–Cas system. Fungal Genet Biol 89:3–9.
https://doi.org/10.1016/j.fgb.2015.09.001
Seidler NW, Jona I, Vegh M, Martonosi A (1989) Cyclopiazonic acid is a specific inhibitor of the Ca2+ATPase of sarcoplasmic reticulum. J Biol Chem
264:17816–17823
Shang Z, Salim AA, Capon RJ (2017) Chaunopyran A:
co-cultivation of marine mollusk-derived fungi
activates a rare class of 2-alkenyl-tetrahydropyran.
J Nat Prod 80:1167–1172. https://doi.org/10.1021/
acs.jnatprod.7b00144
292
M. Flak et al.
interactions trigger the production of antibiotics.
Curr Opin Microbiol 45:117–123. https://doi.org/
10.1016/j.mib.2018.04.002
Nichols D, Cahoon N, Trakhtenberg EM et al (2010)
Use of iChip for high-throughput in situ cultivation of ‘uncultivable’ microbial species. Appl Environ Microbiol 76:2445–2450. https://doi.org/
10.1128/AEM.01754-09
Nielsen ML, Isbrandt T, Petersen LM et al (2016) Linker
flexibility facilitates module exchange in fungal
hybrid PKS-NRPS engineering. PLoS One 11:
e0161199.
https://doi.org/10.1371/journal.
pone.0161199
Nielsen ML, Isbrandt T, Rasmussen KB et al (2017)
Genes linked to production of secondary metabolites in Talaromyces atroroseus revealed using
CRISPR-Cas9. PLoS One 12:e0169712. https://doi.
org/10.1371/journal.pone.0169712
Nødvig CS, Nielsen JB, Kogle ME, Mortensen UH
(2015) A CRISPR-Cas9 system for genetic engineering of filamentous fungi. PLoS One
10:0133085.
https://doi.org/10.1371/journal.
pone.0133085
Oakley CE, Ahuja M, Sun WW et al (2017) Discovery of
McrA, a master regulator of Aspergillus secondary
metabolism. Mol Microbiol 103:347–365. https://
doi.org/10.1111/mmi.13562
Okuda S, Yamada T, Hamajima M et al (2008) KEGG
Atlas mapping for global analysis of metabolic
pathways. Nucleic Acids Res 36:W423–W426.
https://doi.org/10.1093/nar/gkn282
Omura S, Ikeda H, Malpartida F et al (1986) Production
of new hybrid antibiotics, mederrhodins A and B,
by a genetically engineered strain. Antimicrob
Agents Chemother 29:13–19. https://doi.org/
10.1128/AAC.29.1.13
Owen JG, Calcott MJ, Robins KJ, Ackerley DF (2016)
Generating functional recombinant NRPS
enzymes in the laboratory setting via peptidyl carrier protein engineering. Cell Chem Biol 23:1395–
1406.
https://doi.org/10.1016/j.chembiol.2016.09.014
Owens RA, Hammel S, Sheridan KJ et al (2014) A
proteomic approach to investigating gene cluster
expression and secondary metabolite functionality
in Aspergillus fumigatus. PLoS One 9:e106942.
https://doi.org/10.1371/journal.pone.0106942
Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL
(2007) Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug
Discov 6:29–40. https://doi.org/10.1038/nrd2201
Pfannenstiel BT, Zhao X, Wortman J et al (2017) Revitalization of a forward genetic screen identifies
three new regulators of fungal secondary metabolism in the genus Aspergillus. MBio 8:e01246–
e01217. https://doi.org/10.1128/mBio.01246-17
Piechulla B, Degenhardt J (2014) The emerging importance of microbial volatile organic compounds.
Plant Cell Environ 37:811–812. https://doi.org/
10.1111/pce.12254
Robey MT, Ye R, Bok JW et al (2018) Identification of
the first diketomorpholine biosynthetic pathway
using FAC-MS technology. ACS Chem Biol
13:1142–1147. https://doi.org/10.1021/acschembio.8b00024
Robinson SL, Panaccione DG (2014) Heterologous
expression of lysergic acid and novel ergot alkaloids in Aspergillus fumigatus. Appl Environ
Microbiol 80:6465–6472. https://doi.org/10.1128/
AEM.02137-14
Rutledge PJ, Challis GL (2015) Discovery of microbial
natural products by activation of silent biosynthetic gene clusters. Nat Rev Microbiol 13:509–
523. https://doi.org/10.1038/nrmicro3496
Sakai K, Kinoshita H, Shimizu T, Nihira T (2008) Construction of a citrinin gene cluster expression system in heterologous Aspergillus oryzae. J Biosci
Bioeng 106:466–472. https://doi.org/10.1263/
jbb.106.466
Sanchez JF, Somoza AD, Keller NP, Wang CCC (2012)
Advances in Aspergillus secondary metabolite
research in the post-genomic era. Nat Prod Rep
29:351. https://doi.org/10.1039/c2np00084a
Schmidt K, Podmore I (2015) Current challenges in
volatile organic compounds analysis as potential
biomarkers of cancer. J Biomarkers 2015:1–16.
https://doi.org/10.1155/2015/981458
Schmidt-Dannert C (2015) NextGen microbial natural
products discovery. Microb Biotechnol 8:26–28.
https://doi.org/10.1111/1751-7915.12184
Schroeckh V, Scherlach K, Nu ¨tzmann HW et al (2009)
Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus
nidulans. Proc Natl Acad Sci U S A 106:14558–
14563. https://doi.org/10.1073/pnas.0901870106
Schuetze T, Meyer V (2017) Polycistronic gene expression in Aspergillus niger. Microb Cell Factories
16:162. https://doi.org/10.1186/s12934-017-0780-z
Schu ¨mann J, Hertweck C (2006) Advances in cloning,
functional analysis and heterologous expression of
fungal polyketide synthase genes. J Biotechnol
124:690–703.
https://doi.org/10.1016/j.jbiotec.2006.03.046
Schuster M, Schweizer G, Reissmann S, Kahmann R
(2016) Genome editing in Ustilago maydis using
the CRISPR–Cas system. Fungal Genet Biol 89:3–9.
https://doi.org/10.1016/j.fgb.2015.09.001
Seidler NW, Jona I, Vegh M, Martonosi A (1989) Cyclopiazonic acid is a specific inhibitor of the Ca2+ATPase of sarcoplasmic reticulum. J Biol Chem
264:17816–17823
Shang Z, Salim AA, Capon RJ (2017) Chaunopyran A:
co-cultivation of marine mollusk-derived fungi
activates a rare class of 2-alkenyl-tetrahydropyran.
J Nat Prod 80:1167–1172. https://doi.org/10.1021/
acs.jnatprod.7b00144
292
M. Flak et al.