Abstract
Aspergillus niger is widely used as a cell factory for homologous and heterologous protein production. As previous studies reported that reduced sporulation favors protein secretion in A. niger, in this study, we conducted a comparative genomic analysis of the non-sporulating industrially exploited A. niger strain LDM3 in China and the reference protein secretion strain CBS 513.88 to predict the key genes that might define the genetic basis of LDM3’s high protein-producing potential in silico. After sequencing using a hybrid approach combining Illumina and PacBio sequencing platforms, a high-quality genome sequence of LDM3 was obtained which harbors 11,209 open reading frames (ORFs). LDM3 exhibits large chromosomal rearrangements in comparison to CBS 513.88. An alignment of the two genome sequences revealed that the majority of the 457 ORFs uniquely present in LDM3 possessed predicted functions in redox pathways, protein transport, and protein modification processes. In addition, bioinformatic analyses revealed the presence of 656 ORFs in LDM3 with non-synonymous mutations encoding for proteins related to protein translation, protein modification, protein secretion, metabolism, and energy production. We studied the impact of two of these on protein production in the established lab strain N402. Both tupA and prpA genes were selected because available literature suggested their involvement in asexual sporulation of A. niger. Our co-expression network analysis supportively predicted the role of tupA in protein secretion and the role of prpA in energy generation, respectively. By knockout experiments, we showed that the ΔtupA mutant displayed reduced sporulation (35%) accompanied by higher total protein secretion (65%) compared to its parental strain. Such an effect was, however, not observed in the ΔprpA mutant.
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References
Adams TH, Bolan MT, Timberlake WE (1988) BrlA is necessary and sufficient to direct conidiophore development in Aspergillus nidulans. Cell 54:353–362. https://doi.org/10.1016/0092-8674(88)90198-5
Andersen MR, Salazar MP, Schaap PJ, van de Vondervoort PJ, Culley D, Thykaer J, Frisvad JC, Nielsen KF, Albang R, Albermann K, Berka RM, Braus GH, Braus-Stromeyer SA, Corrochano LM, Dai Z, van Dijck PW, Hofmann G, Lasure LL, Magnuson JK, Menke H, Meijer M, Meijer SL, Nielsen JB, Nielsen ML, van Ooyen AJ, Pel HJ, Poulsen L, Samson RA, Stam H, Tsang A, van den Brink JM, Atkins A, Aerts A, Shapiro H, Pangilinan J, Salamov A, Lou Y, Lindquist E, Lucas S, Grimwood J, Grigoriev IV, Kubicek CP, Martinez D, van Peij NN, Roubos JA, Nielsen J, Baker SE (2011) Comparative genomics of citric acid producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88. Genome Res 21:885–897. https://doi.org/10.1101/gr.112169.110
Arentshorst M, Ram AFJ, Meyer V (2012) Using non-homologous end-joining-deficient strains for functional gene analyses in filamentous fungi. Methods Mol Biol 835:133–150. https://doi.org/10.1007/978-1-61779-501-5_9
Ashburner M, Ball CA, Blake JA, Botstein D, Cherry JM (2000) Gene ontology: tool for the unification of biology. Nat Genet 25:25–29. https://doi.org/10.1038/75556
Aufauvre-Brown A, Mellado E, Gow N, Holden D (1997) Aspergillus fumigatus chsE: a gene related to CHS3 of Saccharomyces cerevisiae and important for hyphal growth and conidiophore development but not pathogenicity. Fungal Genet Biol 21:141–152. https://doi.org/10.1006/fgbi.1997.0959
Baker SE (2006) Aspergillus niger genomics: past, present and into the future. Med Mycol 44(Suppl 1):S17–S21. https://doi.org/10.1080/13693780600921037
Basenko EY, Pulman JA, Shanmugasundram A, Harb OS, Crouch K, Starns D, Warrenfeltz S, Aurrecoechea C, Stoeckert CJJ, Kissinger JC, Roos DS, Hertz-Fowler C (2018) FungiDB: an integrated bioinformatic resource for fungi and oomycetes. J Fungi (Basel) 4:39–67. https://doi.org/10.3390/jof4010039
Boecker S, Grätz S, Kerwat D, Adam L, Schirmer D, Richter L, Schütze T, Petras D, Süssmuth RD, Meyer V (2018) Aspergillus niger is a superior expression host for the production of bioactive fungal cyclodepsipeptides. Fungal Biol Biotechnol 5:4–17. https://doi.org/10.1186/s40694-018-0048-3 eCollection 2018
Cairns TC, Nai C, Meyer V (2018) How a fungus shapes biotechnology: 100 years of Aspergillus niger research. Fungal Biol Biotechnol 5:13–27. https://doi.org/10.1186/s40694-018-0054-5
Cairns TC, Zheng X, Zheng P, Sun J, Meyer V (2019) Moulding the mould: understanding and reprogramming filamentous fungal growth and morphogenesis for next generation cell factories. Biotechnol Biofuels 12:77–96. https://doi.org/10.1186/s13068-019-1400-4
Carvalho ND, Arentshorst M, Kwon MJ, Meyer V, Ram AF (2010) Expanding the ku70 toolbox for filamentous fungi: establishment of complementation vectors and recipient strains for advanced gene analyses. Appl Microbiol Biotechnol 87:1463–1473. https://doi.org/10.1007/s00253-010-2588-1
Carvalho ND, Jørgensen TR, Arentshorst M, Nitsche BM, van den Hondel CA, Archer DB, Ram AF (2012) Genome-wide expression analysis upon constitutive activation of the HacA bZIP transcription factor in Aspergillus niger reveals a coordinated cellular response to counteract ER stress. BMC Genomics 13:350–367. https://doi.org/10.1186/1471-2164-13-350
Chen CC, Ghaffari N, Qian X, Yoon BJ (2017) Optimal hybrid sequencing and assembly: feasibility conditions for accurate genome reconstruction and cost minimization strategy. Comput Biol Chem 69:153–163. https://doi.org/10.1016/j.compbiolchem.2017.03.016
de Vries RP, Riley R, Wiebenga A, Aguilar-Osorio G, Amillis S, Uchima CA, Anderluh G, Asadollahi M, Askin M, Barry K, Battaglia E, Bayram O, Benocci T, Braus-Stromeyer SA, Caldana C, Canovas D, Cerqueira GC, Chen F, Chen W, Choi C, Clum A, Dos Santos RA, Damasio AR, Diallinas G, Emri T, Fekete E, Flipphi M, Freyberg S, Gallo A, Gournas C, Habgood R, Hainaut M, Harispe ML, Henrissat B, Hilden KS, Hope R, Hossain A, Karabika E, Karaffa L, Karanyi Z, Krasevec N, Kuo A, Kusch H, LaButti K, Lagendijk EL, Lapidus A, Levasseur A, Lindquist E, Lipzen A, Logrieco AF, MacCabe A, Makela MR, Malavazi I, Melin P, Meyer V, Mielnichuk N, Miskei M, Molnar AP, Mule G, Ngan CY, Orejas M, Orosz E, Ouedraogo JP, Overkamp KM, Park HS, Perrone G, Piumi F, Punt PJ, Ram AF, Ramon A, Rauscher S, Record E, Riano-Pachon DM, Robert V, Rohrig J, Ruller R, Salamov A, Salih NS, Samson RA, Sandor E, Sanguinetti M, Schutze T, Sepcic K, Shelest E, Sherlock G, Sophianopoulou V, Squina FM, Sun H, Susca A, Todd RB, Tsang A, Unkles SE, van de Wiele N, van Rossen-Uffink D, Oliveira JV, Vesth TC, Visser J, Yu JH, Zhou M, Andersen MR, Archer DB, Baker SE, Benoit I, Brakhage AA, Braus GH, Fischer R, Frisvad JC, Goldman GH, Houbraken J, Oakley B, Pocsi I, Scazzocchio C, Seiboth B, vanKuyk PA, Wortman J, Dyer PS, Grigoriev IV (2017) Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus. Genome Biol 18:28–72. https://doi.org/10.1186/s13059-017-1151-0
Fiedler MRM, Cairns TC, Koch O, Kubisch C, Meyer V (2018a) Conditional expression of the small GTPase ArfA impacts secretion, morphology, growth, and actin ring position in Aspergillus niger. Front Microbiol 9:878–894. https://doi.org/10.3389/fmicb.2018.00878
Fiedler MRM, Barthel L, Kubisch C, Nai C, Meyer V (2018b) Construction of an improved Aspergillus niger platform for enhanced glucoamylase secretion. Microb Cell Factories 17:95–106. https://doi.org/10.1186/s12934-018-0941-8
Galperin MY, Makarova KS, Wolf YI, Koonin EV (2014) Expanded microbial genome coverage and improved protein family annotation in the COG database. Nucleic Acids Res 43:D261–D269
Gillingham AK, Tong AHY, Boone C, Munro S (2004) The GTPase Arf1p and the ER to Golgi cargo receptor Erv14p cooperate to recruit the golgin Rud3p to the cis-Golgi. J Cell Biol 167:281–292. https://doi.org/10.1083/jcb.200407088
Gong W, Cheng Z, Zhang H, Liu L, Gao P, Wang L (2016) Draft genome sequence of Aspergillus niger strain An76. Genome Announc 4:e01700–e01715. https://doi.org/10.1128/genomeA.01700-15
Guillemette T, van Peij N, Goosen T, Lanthaler K, Robson GD, van den Hondel CA, Stam H, Archer DB (2007) Genomic analysis of the secretion stress response in the enzyme-producing cell factory Aspergillus niger. BMC Genomics 8:158. https://doi.org/10.1186/1471-2164-8-158
Huerta-Cepas J, Szklarczyk D, Forslund K, Cook H, Heller D, Walter MC, Rattei T, Mende DR, Sunagawa S, Kuhn M, Jensen LJ, von Mering C, Bork P (2015) eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences. Nucleic Acids Res 44:D286–D293. https://doi.org/10.1093/nar/gkv1248
Jimenez-Ortigosa C, Aimanianda V, Muszkieta L, Mouyna I, Alsteens D, Pire S, Beau R, Krappmann S, Beauvais A, Dufrene YF, Roncero C, Latge JP (2012) Chitin synthases with a myosin motor-like domain control the resistance of Aspergillus fumigatus to echinocandins. Antimicrob Agents Chemother 56:6121–6231. https://doi.org/10.1128/AAC.00752-12
Jorgensen TR, Goosen T, Hondel CA, Ram AF, Iversen JJ (2009) Transcriptomic comparison of Aspergillus niger growing on two different sugars reveals coordinated regulation of the secretory pathway. BMC Genomics 10:44. https://doi.org/10.1186/1471-2164-10-44
Jorgensen TR, Nielsen KF, Arentshorst M, Park J, van den Hondel CA, Frisvad JC, Ram AF (2011a) Submerged conidiation and product formation by Aspergillus niger at low specific growth rates are affected in aerial developmental mutants. Appl Environ Microbiol 77:5270–5277. https://doi.org/10.1128/AEM.00118-11
Jorgensen TR, Park J, Arentshorst M, van Welzen AM, Lamers G, Vankuyk PA, Damveld RA, van den Hondel CA, Nielsen KF, Frisvad JC, Ram AF (2011b) The molecular and genetic basis of conidial pigmentation in Aspergillus niger. Fungal Genet Biol 48:544–553. https://doi.org/10.1016/j.fgb.2011.01.005
Krijgsheld P, Nitsche BM, Post H, Levin AM, Muller WH, Heck AJ, Ram AF, Altelaar AF, Wosten HA (2013) Deletion of flbA results in increased secretome complexity and reduced secretion heterogeneity in colonies of Aspergillus niger. J Proteome Res 12:1808–1819. https://doi.org/10.1021/pr301154w
Kumar P, Satyanarayana T (2009) Microbial glucoamylases: characteristics and applications. Crit Rev Biotechnol 29:225–255. https://doi.org/10.1080/07388550903136076
Kurtz S, Phillippy A, Delcher AL, Smoot M, Shumway M, Antonescu C, Salzberg SL (2004) Versatile and open software for comparing large genomes. Genome Biol 5:R12. https://doi.org/10.1186/gb-2004-5-2-r12
Kwon MJ, Jørgensen TR, Nitsche BM, Arentshorst M, Park J, Ram AF, Meyer V (2012) The transcriptomic fingerprint of glucoamylase over-expression in Aspergillus niger. BMC Genomics 13:701–718. https://doi.org/10.1186/1471-2164-13-701
Lee BN, Adams TH (1994) Overexpression of flbA, an early regulator of Aspergillus asexual sporulation, leads to activation of brlA and premature initiation of development. Mol Microbiol 14:323–334. https://doi.org/10.1111/j.1365-2958.1994.tb01293.x
Lee BN, Adams TH (1996) FluG and flbA function interdependently to initiate conidiophore development in Aspergillus nidulans through brlA beta activation. EMBO J 15:299–309. https://doi.org/10.1002/j.1460-2075.1996.tb00360.x
Li H, Durbin R (2010) Fast and accurate long-read alignment with burrows-wheeler transform. Bioinformatics 26:589–595. https://doi.org/10.1093/bioinformatics/btp698
Liu X, Ashforth E, Ren B, Song F, Dai H, Liu M, Wang J, Xie Q, Zhang L (2010) Bioprospecting microbial natural product libraries from the marine environment for drug discovery. J Antibiot 63:415–422. https://doi.org/10.1038/ja.2010.56
Liu X, Bolla K, Ashforth EJ, Zhuo Y, Gao H, Huang P, Stanley SA, Hung DT, Zhang L (2012) Systematics-guided bioprospecting for bioactive microbial natural products. Antonie Van Leeuwenhoek 101:55–66. https://doi.org/10.1007/s10482-011-9671-1
Mah JH, Yu JH (2006) Upstream and downstream regulation of asexual development in Aspergillus fumigatus. Eukaryot Cell 5:1585–1595. https://doi.org/10.1128/EC.00192-06
Mellado E, Aufauvre-Brown A, Gow N, Holden D (1996a) The Aspergillus fumigatus chsC and chsG genes encode class III chitin synthases with different functions. Mol Microbiol 20:667–679. https://doi.org/10.1007/BF00400554
Mellado E, Specht CA, Robbins PW, Holden DW (1996b) Cloning and characterization of chsD, a chitin synthase-like gene of Aspergillus fumigatus. FEMS Microbiol Lett 143:69–76. https://doi.org/10.1111/j.1574-6968.1996.tb08463.x
Mellado E, Dubreucq G, Mol P, Sarfati J, Paris S, Diaquin M, Holden DW, Rodriguez-Tudela JL, Latge JP (2003) Cell wall biogenesis in a double chitin synthase mutant (chsG−/chsE-) of Aspergillus fumigatus. Fungal Genet Biol 38:98–109. https://doi.org/10.1016/s1087-1845(02)00516-9
Minoru K, Yoko S, Masayuki K, Miho F, Mao T (2015) KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res 44:D457–D462. https://doi.org/10.1093/nar/gkv1070
Mouyna I, Morelle W, Vai M, Monod M, Lechenne B, Fontaine T, Beauvais A, Sarfati J, Prevost MC, Henry C, Latge JP (2005) Deletion of GEL2 encoding for a beta(1-3)glucanosyltransferase affects morphogenesis and virulence in Aspergillus fumigatus. Mol Microbiol 56:1675–1688. https://doi.org/10.1111/j.1365-2958.2005.04654.x
Nakamura T, Maeda Y, Tanoue N, Makita T, Kato M, Kobayashi T (2006) Expression profile of amylolytic genes in Aspergillus nidulans. Biosci Biotechnol Biochem 70:2363–2370. https://doi.org/10.1271/bbb.50694
Park J, Park J, Jang S, Kim S, Kong S, Choi J, Ahn K, Kim J, Lee S, Kim S, Park B, Jung K, Kim S, Kang S, Lee YH (2008) FTFD: an informatics pipeline supporting phylogenomic analysis of fungal transcription factors. Bioinformatics 24:1024–1025. https://doi.org/10.1093/bioinformatics/btn058
Paul S, Ludena Y, Villena GK, Yu F, Sherman DH, Gutierrez-Correa M (2017) High-quality draft genome sequence of a biofilm forming lignocellulolytic Aspergillus niger strain ATCC 10864. Stand Genomic Sci 12:37–45. https://doi.org/10.1186/s40793-017-0254-2
Pavezzi FC, Carneiro AA, Bocchini-Martins DA, Alves-Prado HF, Ferreira H, Martins PM, Gomes E, da Silva R (2011) Influence of different substrates on the production of a mutant thermostable glucoamylase in submerged fermentation. Appl Biochem Biotechnol 163:14–24. https://doi.org/10.1007/s12010-010-8963-7
Pel HJ, de Winde JH, Archer DB, Dyer PS, Hofmann G, Schaap PJ, Turner G, de Vries RP, Albang R, Albermann K, Andersen MR, Bendtsen JD, Benen JA, van den Berg M, Breestraat S, Caddick MX, Contreras R, Cornell M, Coutinho PM, Danchin EG, Debets AJ, Dekker P, van Dijck PW, van Dijk A, Dijkhuizen L, Driessen AJ, d'Enfert C, Geysens S, Goosen C, Groot GS, de Groot PW, Guillemette T, Henrissat B, Herweijer M, van den Hombergh JP, van den Hondel CA, van der Heijden RT, van der Kaaij RM, Klis FM, Kools HJ, Kubicek CP, van Kuyk PA, Lauber J, Lu X, van der Maarel MJ, Meulenberg R, Menke H, Mortimer MA, Nielsen J, Oliver SG, Olsthoorn M, Pal K, van Peij NN, Ram AF, Rinas U, Roubos JA, Sagt CM, Schmoll M, Sun J, Ussery D, Varga J, Vervecken W, van de Vondervoort PJ, Wedler H, Wosten HA, Zeng AP, van Ooyen AJ, Visser J, Stam H (2007) Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88. Nat Biotechnol 25:221–231. https://doi.org/10.1038/nbt1282
Perez-de-Nanclares-Arregi E, Etxebeste O (2014) Photo-convertible tagging for localization and dynamic analyses of low-expression proteins in filamentous fungi. Fungal Genet Biol 70:33–41. https://doi.org/10.1016/j.fgb.2014.06.006
Rhoads A, Au KF (2015) PacBio sequencing and its applications. Genom Proteom Bioinf 13:278–289. https://doi.org/10.1016/j.gpb.2015.08.002
Rogg LE, Fortwendel JR, Juvvadi PR, Lilley A, Steinbach WJ (2011) The chitin synthase genes chsA and chsC are not required for cell wall stress responses in the human pathogen Aspergillus fumigatus. Biochem Biophys Res Commun 411:549–554. https://doi.org/10.1016/j.bbrc.2011.06.180
Schachtschabel D, Arentshorst M, Nitsche BM, Morris S, Nielsen KF, van den Hondel CA, Klis FM, Ram AF (2013) The transcriptional repressor TupA in Aspergillus niger is involved in controlling gene expression related to cell wall biosynthesis, development, and nitrogen source availability. PLoS One 8:e78102. https://doi.org/10.1371/journal.pone.0078102
Schape P, Kwon MJ, Baumann B, Gutschmann B, Jung S, Lenz S, Nitsche B, Paege N, Schutze T, Cairns TC, Meyer V (2019) Updating genome annotation for the microbial cell factory Aspergillus niger using gene co-expression networks. Nucleic Acids Res 47:559–569. https://doi.org/10.1093/nar/gky1183
Swift RJ, Wiebe MG, Robson GD, Trinci APJ (1998) Recombinant glucoamylase production by Aspergillus niger B1 in chemostat and pH auxostat cultures. Fungal Genet Biol 25:100–109. https://doi.org/10.1006/fgbi.1998.1089
Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, Jensen LJ, von Mering C (2017) The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res 45:D362–D368. https://doi.org/10.1093/nar/gkw937
Takeshita N, Ohta A, Horiuchi H (2002) csmA, a gene encoding a class V chitin synthase with a myosin motor-like domain of Aspergillus nidulans, is translated as a single polypeptide and regulated in response to osmotic conditions. Biochem Biophys Res Commun 298:103–109. https://doi.org/10.1016/s0006-291x(02)02418-x
Takeshita N, Ohta A, Horiuchi H (2005) CsmA, a class V chitin synthase with a myosin motor-like domain, is localized through direct interaction with the actin cytoskeleton in Aspergillus nidulans. Mol Biol Cell 16:1961–1970. https://doi.org/10.1091/mbc.e04-09-0761
te Biesebeke R, van Biezen N, de Vos W, van den Hondel C, Punt PJ (2005) Different control mechanisms regulate glucoamylase and protease gene transcription in Aspergillus oryzae in solid-state and submerged fermentation. Appl Microbiol Biotechnol 67:75–82. https://doi.org/10.1007/s00253-004-1807-z
van Munster JM, Nitsche BM, Akeroyd M, Dijkhuizen L, van der Maarel MJ, Ram AF (2015) Systems approaches to predict the functions of glycoside hydrolases during the life cycle of Aspergillus niger using developmental mutants brlA and flbA. PLoS One 10:e0116269. https://doi.org/10.1371/journal.pone.0116269
Vesth TC, Nybo JL, Theobald S, Frisvad JC, Larsen TO, Nielsen KF, Hoof JB, Brandl J, Salamov A, Riley R, Gladden JM, Phatale P, Nielsen MT, Lyhne EK, Kogle ME, Strasser K, McDonnell E, Barry K, Clum A, Chen C, LaButti K, Haridas S, Nolan M, Sandor L, Kuo A, Lipzen A, Hainaut M, Drula E, Tsang A, Magnuson JK, Henrissat B, Wiebenga A, Simmons BA, Makela MR, de Vries RP, Grigoriev IV, Mortensen UH, Baker SE, Andersen MR (2018) Investigation of inter- and intraspecies variation through genome sequencing of Aspergillus section Nigri. Nat Genet 50:1688–1695. https://doi.org/10.1038/s41588-018-0246-1
Vongsangnak W, Hansen K, Nielsen J (2011) Integrated analysis of the global transcriptional response to alpha-amylase over-production by Aspergillus oryzae. Biotechnol Bioeng 108:1130–1139. https://doi.org/10.1002/bit.23033
Wanka F, Cairns T, Boecker S, Berens C, Happel A, Zheng X, Sun J, Krappmann S, Meyer V (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
Wanke C, Eckert S, Albrecht G, van Hartingsveldt W, Punt PJ, van den Hondel CAMJJ, Braus GH (1997) The Aspergillus niger GCN4 homologue, cpcA, is transcriptionally regulated and encodes an unusual leucine zipper. Mol Microbiol 23:23–33. https://doi.org/10.1046/j.1365-2958.1997.1741549.x
Wieser J, Lee BN, Fondon J 3rd, Adams TH (1994) Genetic requirements for initiating asexual development in Aspergillus nidulans. Curr Genet 27:62–69. https://doi.org/10.1007/bf00326580
Wolf J, Nicks M, Deitz S, Ev T, Franzusoff A (1998) An N-end rule destabilization mutant reveals pre-Golgi requirements for Sec7p in yeast membrane traffic. Biochem Biophs Res Commun 243:191–198. https://doi.org/10.1006/bbrc.1998.8084
Yamada O, Lee BR, Gomi K, Iimura Y (1999) Cloning and functional analysis of the Aspergillus oryzae conidiation regulator gene brZA by its disruption and misscheduled expression. J Biosci Bioeng 87:424–429. https://doi.org/10.1016/S1389-1723(99)80089-9
Yamashiroy CT, Ebbole DJ, Lee BU, Brown RE, Bourland C, Madi L, Yanofsky C (1996) Characterization of rco-1 of Neurospora crassa, a pleiotropic gene affecting growth and development that encodes a homolog of Tup1 of Saccharomyces cerevisiae. Mol Cell Biol 16:6218–6228. https://doi.org/10.1128/mcb.16.11.6218
Yin C, Wang B, He P, Lin Y, Pan L (2014) Genomic analysis of the aconidial and high-performance protein producer, industrially relevant Aspergillus niger SH2 strain. Gene 541:107–114. https://doi.org/10.1016/j.gene.2014.03.011
Yin X, Shin HD, Li J, Du G, Liu L, Chen J (2017) Comparative genomics and transcriptome analysis of Aspergillus niger and metabolic engineering for citrate production. Sci Rep 7:41040–41057. https://doi.org/10.1038/srep41040
Yuan XL, van der Kaaij RM, van den Hondel CA, Punt PJ, van der Maarel MJ, Dijkhuizen L, Ram AF (2008) Aspergillus niger genome-wide analysis reveals a large number of novel alpha-glucan acting enzymes with unexpected expression profiles. Mol Gen Genomics 279:545–561. https://doi.org/10.1007/s00438-008-0332-7
Zhang C, Meng X, Wei X, Lu L (2016) Highly efficient CRISPR mutagenesis by microhomology-mediated end joining in Aspergillus fumigatus. Fungal Genet Biol 86:47–57. https://doi.org/10.1016/j.fgb.2015.12.007
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Yufei Sui is grateful for a joint-PhD fellowship by the Chinese scholarship council.
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This work was funded by the Basic Research Program of Shenzhen (JCYJ20150629165423751) and the Fundamental Research Funds for the Central Universities No. 22221818014.
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YFS, LMO, and SC performed the genomics analyses and executed in silico quality analyses. YFS and TS constructed the co-expression networks. YFS and TS generated deletion strains and characterized them. YPZ and VM initiated this study and coordinated the project. YFS, LMO, TS and VM co-wrote the final text. All authors read and approved the final manuscript.
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Sui, YF., Ouyang, LM., Schütze, T. et al. Comparative genomics of the aconidial Aspergillus niger strain LDM3 predicts genes associated with its high protein secretion capacity. Appl Microbiol Biotechnol 104, 2623–2637 (2020). https://doi.org/10.1007/s00253-020-10398-1
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DOI: https://doi.org/10.1007/s00253-020-10398-1