Hess GT, Fre ´sard L, Han K, Lee CH, Li A, Cimprich KA,
Montgomery SB, Bassik MC (2016) Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells. Nat Methods 13:1036–
1042
Hoang HD, Maruyama JI, Kitamoto K (2015) Modulating endoplasmic reticulum-Golgi cargo receptors
for improving secretion of carrier-fused heterologous proteins in the filamentous fungus Aspergillus oryzae. Appl Environ Microbiol 81:533–543
Hoefgen S, Lin J, Fricke J, Stroe MC, Mattern DJ, Kufs
JE, Hortschansky P, Brakhage AA, Hoffmeister D,
Valiante V (2018) Facile assembly and
fluorescence-based screening method for heterologous expression of biosynthetic pathways in
fungi. Metab Eng 48:44–51
Holm DMK (2013) Development and implementation
of novel genetic tools for investigation of fungal
secondary metabolism. PhD thesis, Technical University of Denmark
Holm DK, Petersen LM, Klitgaard A, Knudsen PB, Jarczynska ZD, Nielsen KF, Gotfredsen CH, Larsen TO,
Mortensen UH (2014) Molecular and chemical
characterization of the biosynthesis of the 6MSA-derived meroterpenoid yanuthone D in
Aspergillus niger. Chem Biol 21:519–529
Hoover DM, Lubkowski J (2002) DNAWorks: an
automated method for designing oligonucleotides
for PCR-based gene synthesis. Nucleic Acids Res
30:1–7
Hopp TP, Prickett KS, Price VL, Libby RT, March CJ,
Cerretti DP, Urdal DL, Conlon PJ (1988) A short
polypeptide marker sequence useful for recombinant protein identification and purification. Bio/
Technology 6:1204–1210
Hoshida H, Fujita T, Murata K, Kubo K, Akada R (2005)
Copper-dependent production of a Pycnoporus
coccineus extracellular laccase in Aspergillus oryzae and Saccharomyces cerevisiae. Biosci Biotechnol Biochem 69:1090–1097
Hoskins I, Roberts C (1994) Expression of the 3phosphoglycerate kinase gene (pgkA) of Penicillium chrysogenum. Mol Gen Genet 243:270–276
Hurley JM, Chen CH, Loros JJ, Dunlap JC (2012) Lightinducible system for tunable protein expression in
Neurospora crassa. G3 2:1207–1212
Hynes MJ, Pateman JAJ (1970) The genetic analysis of
regulation of amidase synthesis in Aspergillus
nidulans. Mol Gen Genet 108:107–116
Ilme ´n M, Onnela ML, Klemsdal S, Kera ¨nen S, Penttila ¨ M
(1998) Functional analysis of the cellobiohydrolase
I promoter of the filamentous fungus Trichoderma
reesei. Mol Gen Genet 253:303–314
Iriarte A, Sanguinetti M, Ferna ´ndez-Calero T, Naya H,
Ramo ´n A, Musto H (2012) Translational selection
on codon usage in the genus Aspergillus. Gene
506:98–105
Ishida H, Hata Y, Kawato A, Abe Y, Kashiwagi Y (2004)
Isolation of a novel promoter for efficient protein
production in Aspergillus oryzae. Biosci Biotechnol Biochem 68:1849–1857
Ishii N, Minami N, Chen EY, Medina AL, Chico MM,
Kasamatsu H (1996) Analysis of a nuclear localization signal of simian virus 40 major capsid protein Vp1. J Virol 70:1317–1322
Jackson DC, Tang XL, Brown LE, Murray JM, White
DO, Tregear GW (1986) Antigenic determinants of
influenza virus hemagglutinin XII. Virology
155:625–632
Jalving R, Van De Vondervoort PJI, Visser J, Schaap PJ
(2000) Characterization of the kexin-like maturase
of Aspergillus niger. Appl Environ Microbiol
66:363–368
Jensen ED, Ferreira R, Jakoc ˇiunas T, Arsovska D, Zhang
J, Ding L, Smith JD, David F, Nielsen J, Jensen MK,
Keasling JD (2017) Transcriptional reprogramming in yeast using dCas9 and combinatorial
gRNA strategies. Microb Cell Factories 16:1–16
Jin FJ, Maruyama J, Juvvadi PR, Arioka M, Kitamoto K
(2004) Adenine auxotrophic mutants of Aspergillus oryzae: development of a novel transformation
system with triple auxotrophic hosts. Biosci Biotechnol Biochem 68:656–662
Jin FJ, Watanabe T, Juvvadi PR, Maruyama JI, Arioka M,
Kitamoto K (2007) Double disruption of the proteinase genes, tppA and pepE, increases the production level of human lysozyme by Aspergillus
oryzae. Appl Microbiol Biotechnol 76:1059–1068
Johnstone IL, Hughes SG, Clutterbuck AJ (1985) Cloning an Aspergillus nidulans developmental gene by
transformation. EMBO J 4:1307–1311
Jørgensen TR, Park J, Arentshorst M, van Welzen AM,
Lamers G, VanKuyk PA, Damveld RA, van den
Hondel CAM, Nielsen KF, Frisvad JC, Ram AFJ
(2011) The molecular and genetic basis of conidial
pigmentation in Aspergillus niger. Fungal Genet
Biol 48:544–553
Kamaruddin N, Storms R, Mahadi NM, Illias RM, Bakar
FDA, Murad AMA (2018) Reduction of extracellular proteases increased activity and stability of
heterologous protein in Aspergillus niger. Arab J
Sci Eng 43:3327–3338
Keller NP (2019) Fungal secondary metabolism: regulation, function and drug discovery. Nat Rev Microbiol 17:167–180
Keller NP, Turner G, Bennett JW (2005) Fungal secondary metabolism—from biochemistry to genomics.
Nat Rev Microbiol 3:937–947
Kelly JM, Hynes MJ (1985) Transformation of Aspergillus niger by the amdS gene of Aspergillus nidulans.
EMBO J 4:475–479
Kempken F (2013) Alternative splicing in ascomycetes.
Appl Microbiol Biotechnol 97:4235–4241
Kempken F, Windhofer F (2004) Alternative splicing of
transcripts of the transposon Restless is maintained in the foreign host Neurospora crassa and
can be modified by introducing mutations at the 5
0
and 3
0 splice sites. Curr Genet 46:59–65
10 Filamentous Fungi as Hosts for Heterologous Production of Proteins and Secondary. . .
259
Montgomery SB, Bassik MC (2016) Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells. Nat Methods 13:1036–
1042
Hoang HD, Maruyama JI, Kitamoto K (2015) Modulating endoplasmic reticulum-Golgi cargo receptors
for improving secretion of carrier-fused heterologous proteins in the filamentous fungus Aspergillus oryzae. Appl Environ Microbiol 81:533–543
Hoefgen S, Lin J, Fricke J, Stroe MC, Mattern DJ, Kufs
JE, Hortschansky P, Brakhage AA, Hoffmeister D,
Valiante V (2018) Facile assembly and
fluorescence-based screening method for heterologous expression of biosynthetic pathways in
fungi. Metab Eng 48:44–51
Holm DMK (2013) Development and implementation
of novel genetic tools for investigation of fungal
secondary metabolism. PhD thesis, Technical University of Denmark
Holm DK, Petersen LM, Klitgaard A, Knudsen PB, Jarczynska ZD, Nielsen KF, Gotfredsen CH, Larsen TO,
Mortensen UH (2014) Molecular and chemical
characterization of the biosynthesis of the 6MSA-derived meroterpenoid yanuthone D in
Aspergillus niger. Chem Biol 21:519–529
Hoover DM, Lubkowski J (2002) DNAWorks: an
automated method for designing oligonucleotides
for PCR-based gene synthesis. Nucleic Acids Res
30:1–7
Hopp TP, Prickett KS, Price VL, Libby RT, March CJ,
Cerretti DP, Urdal DL, Conlon PJ (1988) A short
polypeptide marker sequence useful for recombinant protein identification and purification. Bio/
Technology 6:1204–1210
Hoshida H, Fujita T, Murata K, Kubo K, Akada R (2005)
Copper-dependent production of a Pycnoporus
coccineus extracellular laccase in Aspergillus oryzae and Saccharomyces cerevisiae. Biosci Biotechnol Biochem 69:1090–1097
Hoskins I, Roberts C (1994) Expression of the 3phosphoglycerate kinase gene (pgkA) of Penicillium chrysogenum. Mol Gen Genet 243:270–276
Hurley JM, Chen CH, Loros JJ, Dunlap JC (2012) Lightinducible system for tunable protein expression in
Neurospora crassa. G3 2:1207–1212
Hynes MJ, Pateman JAJ (1970) The genetic analysis of
regulation of amidase synthesis in Aspergillus
nidulans. Mol Gen Genet 108:107–116
Ilme ´n M, Onnela ML, Klemsdal S, Kera ¨nen S, Penttila ¨ M
(1998) Functional analysis of the cellobiohydrolase
I promoter of the filamentous fungus Trichoderma
reesei. Mol Gen Genet 253:303–314
Iriarte A, Sanguinetti M, Ferna ´ndez-Calero T, Naya H,
Ramo ´n A, Musto H (2012) Translational selection
on codon usage in the genus Aspergillus. Gene
506:98–105
Ishida H, Hata Y, Kawato A, Abe Y, Kashiwagi Y (2004)
Isolation of a novel promoter for efficient protein
production in Aspergillus oryzae. Biosci Biotechnol Biochem 68:1849–1857
Ishii N, Minami N, Chen EY, Medina AL, Chico MM,
Kasamatsu H (1996) Analysis of a nuclear localization signal of simian virus 40 major capsid protein Vp1. J Virol 70:1317–1322
Jackson DC, Tang XL, Brown LE, Murray JM, White
DO, Tregear GW (1986) Antigenic determinants of
influenza virus hemagglutinin XII. Virology
155:625–632
Jalving R, Van De Vondervoort PJI, Visser J, Schaap PJ
(2000) Characterization of the kexin-like maturase
of Aspergillus niger. Appl Environ Microbiol
66:363–368
Jensen ED, Ferreira R, Jakoc ˇiunas T, Arsovska D, Zhang
J, Ding L, Smith JD, David F, Nielsen J, Jensen MK,
Keasling JD (2017) Transcriptional reprogramming in yeast using dCas9 and combinatorial
gRNA strategies. Microb Cell Factories 16:1–16
Jin FJ, Maruyama J, Juvvadi PR, Arioka M, Kitamoto K
(2004) Adenine auxotrophic mutants of Aspergillus oryzae: development of a novel transformation
system with triple auxotrophic hosts. Biosci Biotechnol Biochem 68:656–662
Jin FJ, Watanabe T, Juvvadi PR, Maruyama JI, Arioka M,
Kitamoto K (2007) Double disruption of the proteinase genes, tppA and pepE, increases the production level of human lysozyme by Aspergillus
oryzae. Appl Microbiol Biotechnol 76:1059–1068
Johnstone IL, Hughes SG, Clutterbuck AJ (1985) Cloning an Aspergillus nidulans developmental gene by
transformation. EMBO J 4:1307–1311
Jørgensen TR, Park J, Arentshorst M, van Welzen AM,
Lamers G, VanKuyk PA, Damveld RA, van den
Hondel CAM, Nielsen KF, Frisvad JC, Ram AFJ
(2011) The molecular and genetic basis of conidial
pigmentation in Aspergillus niger. Fungal Genet
Biol 48:544–553
Kamaruddin N, Storms R, Mahadi NM, Illias RM, Bakar
FDA, Murad AMA (2018) Reduction of extracellular proteases increased activity and stability of
heterologous protein in Aspergillus niger. Arab J
Sci Eng 43:3327–3338
Keller NP (2019) Fungal secondary metabolism: regulation, function and drug discovery. Nat Rev Microbiol 17:167–180
Keller NP, Turner G, Bennett JW (2005) Fungal secondary metabolism—from biochemistry to genomics.
Nat Rev Microbiol 3:937–947
Kelly JM, Hynes MJ (1985) Transformation of Aspergillus niger by the amdS gene of Aspergillus nidulans.
EMBO J 4:475–479
Kempken F (2013) Alternative splicing in ascomycetes.
Appl Microbiol Biotechnol 97:4235–4241
Kempken F, Windhofer F (2004) Alternative splicing of
transcripts of the transposon Restless is maintained in the foreign host Neurospora crassa and
can be modified by introducing mutations at the 5
0
and 3
0 splice sites. Curr Genet 46:59–65
10 Filamentous Fungi as Hosts for Heterologous Production of Proteins and Secondary. . .
259