Enhanced citric acid production in aspergillus with inactivated asparagine-linked glycosylation protein 3 (ALG3), and/or increased laeA expression

Dai, Ziyu; Baker, Scott E.

Title: Enhanced citric acid production in aspergillus with inactivated asparagine-linked glycosylation protein 3 (ALG3), and/or increased laeA expression

Patent · Tue Dec 08 00:00:00 EST 2015

OSTI ID:1228371

Dai, Ziyu; Baker, Scott E.

Provided herein are fungi, such as Aspergillus niger, having a dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase (Alg3) gene genetic inactivation, increased expression of a loss of aflR expression A (Lae), or both. In some examples, such mutants have several phenotypes, including an increased production of citric acid relative to the parental strain. Methods of using the disclosed fungi to make citric acid are also provided, as are compositions and kits including the disclosed fungi.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

Assignee:: Battelle Memorial Institute

Patent Number(s):: 9,206,450

Application Number:: 14/703,499

OSTI ID:: 1228371

Resource Relation:: Patent File Date: 2015 May 04

Country of Publication:: United States

Language:: English

References (63)

Process for producing of citric acid and monovalent citrate salts Datta, Rathin; Bergemann, Eugene P. https://doi.org/https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/5532148 US Patent Document 5,532,148	patent	July 1996
Global regulator of secondary metabolite biosynthesis and methods of use Keller, Nancy P.; Bok, Jin Woo https://doi.org/https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/20040058872 US Patent Application 10/668696; 20040058872	patent-application	March 2004
Novel Hansenula Polymorpha Gene Coding for Dolichyl-Phosphate- Mannose Dependent Alpha-1,3 Mannosyltransferase and Process for the Production of Recombinant Glycoproteins With Hansenula Polymorpha Mutant Strain Deficient in Kang, Hyun Ah; Park, Jeong Seok; Kim, Moo Woong https://doi.org/https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/20100062485 US Patent Application 12/091217; 20100062485	patent-application	March 2010
Cloning and characterization of the ALG3 gene of Saccharomyces cerevisiae Aebi, Markus; Gassenhuber, Johann; Domdey, Horst Glycobiology, Vol. 6, Issue 4, p. 439-444 https://doi.org/10.1093/glycob/6.4.439	journal	January 1996
Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88 Andersen, M. R.; Salazar, M. P.; Schaap, P. J. Genome Research, Vol. 21, Issue 6, p. 885-897 https://doi.org/10.1101/gr.112169.110	journal	May 2011
On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database Apweiler, Rolf; Hermjakob, Henning; Sharon, Nathan Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1473, Issue 1, p. 4-8 https://doi.org/10.1016/S0304-4165(99)00165-8	journal	December 1999
Identification and characterization of Penicillium citrinum VeA and LaeA as global regulators for ML-236B production Baba, Satoshi; Kinoshita, Hiroshi; Nihira, Takuya Current Genetics, Vol. 58, Issue 1, p. 1-11 https://doi.org/10.1007/s00294-011-0359-x	journal	December 2011
VelB/VeA/LaeA Complex Coordinates Light Signal with Fungal Development and Secondary Metabolism Bayram, O.; Krappmann, S.; Ni, M. Science, Vol. 320, Issue 5882, p. 1504-1506 https://doi.org/10.1126/science.1155888	journal	June 2008
LaeA Control of Velvet Family Regulatory Proteins for Light-Dependent Development and Fungal Cell-Type Specificity Sarikaya Bayram, Özlem; Bayram, Özgür; Valerius, Oliver PLoS Genetics, Vol. 6, Issue 12, Article No. e1001226 https://doi.org/10.1371/journal.pgen.1001226	journal	December 2010
LaeA, a Regulator of Secondary Metabolism in Aspergillus spp. Bok, Jin Woo; Keller, Nancy P. Eukaryotic Cell, Vol. 3, Issue 2, p. 527-535 https://doi.org/10.1128/EC.3.2.527-535.2004	journal	April 2004
Secondary metabolic gene cluster silencing in Aspergillus nidulans Bok, Jin Woo; Noordermeer, Daan; Kale, Shubha P. Molecular Microbiology, Vol. 61, Issue 6, p. 1636-1645 https://doi.org/10.1111/j.1365-2958.2006.05330.x	journal	September 2006
Chromatin-level regulation of biosynthetic gene clusters Bok, Jin Woo; Chiang, Yi-Ming; Szewczyk, Edyta Nature Chemical Biology, Vol. 5, Issue 7, p. 462-464 https://doi.org/10.1038/nchembio.177	journal	May 2009
Accurate prediction of the Aspergillus nidulans terrequinone gene cluster boundaries using the transcriptional regulator LaeA Bouhired, Sarah; Weber, Monika; Kempf-Sontag, Anita Fungal Genetics and Biology, Vol. 44, Issue 11, p. 1134-1145 https://doi.org/10.1016/j.fgb.2006.12.010	journal	November 2007
Mutational Analysis of the Glycosylphosphatidylinositol (GPI) Anchor Pathway Demonstrates that GPI-Anchored Proteins Are Required for Cell Wall Biogenesis and Normal Hyphal Growth in Neurospora crassa Bowman, Shaun M.; Piwowar, Amy; Al Dabbous, Mash'el Eukaryotic Cell, Vol. 5, Issue 3, p. 587-600 https://doi.org/10.1128/EC.5.3.587-600.2006	journal	March 2006
Lae1 regulates expression of multiple secondary metabolite gene clusters in Fusarium verticillioides Butchko, Robert A. E.; Brown, Daren W.; Busman, Mark Fungal Genetics and Biology, Vol. 49, Issue 8, p. 602-612 https://doi.org/10.1016/j.fgb.2012.06.003	journal	August 2012
The VeA regulatory system and its role in morphological and chemical development in fungi Calvo, Ana M. Fungal Genetics and Biology, Vol. 45, Issue 7, p. 1053-1061 https://doi.org/10.1016/j.fgb.2008.03.014	journal	July 2008
Functional analysis of the ALG3 gene encoding the Dol-P-Man: Man5GlcNAc2-PP-Dol mannosyltransferase enzyme of P. pastoris Davidson, Robert C.; Nett, Juergen H.; Renfer, Eduard Glycobiology, Vol. 14, Issue 5, p. 399-407 https://doi.org/10.1093/glycob/cwh023	journal	January 2004
A plant DNA minipreparation: Version II Dellaporta, Stephen L.; Wood, Jonathan; Hicks, James B. Plant Molecular Biology Reporter, Vol. 1, Issue 4, p. 19-21 https://doi.org/10.1007/BF02712670	journal	September 1983
Congenital Disorder of Glycosylation Type Id: Clinical Phenotype, Molecular Analysis, Prenatal Diagnosis, and Glycosylation of Fetal Proteins Denecke, Jonas; Kranz, Christian; Von Kleist-Retzow, Juergen Ch. Pediatric Research, Vol. 58, Issue 2, p. 248-253 https://doi.org/10.1203/01.PDR.0000169963.94378.B6	journal	August 2005
Proteomics of industrial fungi: trends and insights for biotechnology de Oliveira, José Miguel P. Ferreira; de Graaff, Leo H. Applied Microbiology and Biotechnology, Vol. 89, Issue 2, p. 225-237 https://doi.org/10.1007/s00253-010-2900-0	journal	October 2010
Protein glycosylation pathways in filamentous fungi Deshpande, Nandan; Wilkins, Marc R.; Packer, Nicolle Glycobiology, Vol. 18, Issue 8, p. 626-637 https://doi.org/10.1093/glycob/cwn044	journal	May 2008
Beyond aflatoxin: four distinct expression patterns and functional roles associated with Aspergillus flavus secondary metabolism gene clusters Georgianna, D. Ryan; Fedorova, Natalie D.; Burroughs, James L. Molecular Plant Pathology, Vol. 11, Issue 2, p. 213-226 https://doi.org/10.1111/j.1364-3703.2009.00594.x	journal	March 2010
Advances in the production of human therapeutic proteins in yeasts and filamentous fungi Gerngross, Tillman U. Nature Biotechnology, Vol. 22, Issue 11, p. 1409-1414 https://doi.org/10.1038/nbt1028	journal	November 2004
Genomics of protein folding in the endoplasmic reticulum, secretion stress and glycosylation in the aspergilli Geysens, Steven; Whyteside, Graham; Archer, David B. Fungal Genetics and Biology, Vol. 46, Issue 1, p. S121-S140 https://doi.org/10.1016/j.fgb.2008.07.016	journal	March 2009
Role of Glycosylation in Development Haltiwanger, Robert S.; Lowe, John B. Annual Review of Biochemistry, Vol. 73, Issue 1, p. 491-537 https://doi.org/10.1146/annurev.biochem.73.011303.074043	journal	June 2004
Effective lead selection for improved protein production in Aspergillus niger based on integrated genomics Jacobs, Denise I.; Olsthoorn, Maurien M. A.; Maillet, Isabelle Fungal Genetics and Biology, Vol. 46, Issue 1, p. S141-S152 https://doi.org/10.1016/j.fgb.2008.08.012	journal	March 2009
N-Glycan Modification in Aspergillus Species Kainz, E.; Gallmetzer, A.; Hatzl, C. Applied and Environmental Microbiology, Vol. 74, Issue 4, p. 1076-1086 https://doi.org/10.1128/AEM.01058-07	journal	December 2007
Requirement of LaeA for secondary metabolism and sclerotial production in Aspergillus flavus Kale, Shubha P.; Milde, Lane; Trapp, Marisa K. Fungal Genetics and Biology, Vol. 45, Issue 10, p. 1422-1429 https://doi.org/10.1016/j.fgb.2008.06.009	journal	October 2008
Arabidopsis thaliana ALG3 mutant synthesizes immature oligosaccharides in the ER and accumulates unique N-glycans Kajiura, H.; Seki, T.; Fujiyama, K. Glycobiology, Vol. 20, Issue 6, p. 736-751 https://doi.org/10.1093/glycob/cwq028	journal	March 2010
LaeA, a global regulator of Aspergillus toxins Keller, Nancy; Bok, Jinwoo; Chung, Dawoon Medical Mycology, Vol. 44, Issue s1, p. 83-85 https://doi.org/10.1080/13693780600835773	journal	January 2006
Centralized Modularity of N-Linked Glycosylation Pathways in Mammalian Cells Kim, Pan-Jun; Lee, Dong-Yup; Jeong, Hawoong PLoS ONE, Vol. 4, Issue 10, Article No. e7317 https://doi.org/10.1371/journal.pone.0007317	journal	October 2009
Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl‐P‐Man:Man₅ GlcNAc₂‐PP‐dolichyl mannosyltransferase Körner, Christian; Knauer, Roland; Stephani, Ulrich The EMBO Journal, Vol. 18, Issue 23, p. 6816-6822 https://doi.org/10.1093/emboj/18.23.6816	journal	December 1999
Assembly of Asparagine-Linked Oligosaccharides Kornfeld, R.; Kornfeld, S. Annual Review of Biochemistry, Vol. 54, Issue 1, p. 631-664 https://doi.org/10.1146/annurev.bi.54.070185.003215	journal	June 1985
Approaching the Secrets of N-Glycosylation in Aspergillus fumigatus: Characterization of the AfOch1 Protein Kotz, Andrea; Wagener, Johannes; Engel, Jakob PLoS ONE, Vol. 5, Issue 12, Article No. e15729 https://doi.org/10.1371/journal.pone.0015729	journal	December 2010
CDG-Id in two siblings with partially different phenotypes Kranz, Christian; Sun, Liangwu; Eklund, Erik A. American Journal of Medical Genetics Part A, Vol. 143A, Issue 13, p. 1414-1420 https://doi.org/10.1002/ajmg.a.31796	journal	January 2007
Protein Glycosylation in Yeast Kukuruzinska, M. A.; Bergh, M. L. E.; Jackson, B. J. Annual Review of Biochemistry, Vol. 56, Issue 1, p. 915-944 https://doi.org/10.1146/annurev.bi.56.070187.004411	journal	June 1987
α-1,6-Mannosylation of N-Linked Oligosaccharide Present on Cell Wall Proteins Is Required for Their Incorporation into the Cell Wall in the Filamentous Fungus Neurospora crassa Maddi, Abhiram; Free, Stephen J. Eukaryotic Cell, Vol. 9, Issue 11, p. 1766-1775 https://doi.org/10.1128/EC.00134-10	journal	September 2010
Deletion of the TbALG3 gene demonstrates site-specific N-glycosylation and N-glycan processing in Trypanosoma brucei Manthri, Sujatha; Güther, M. Lucia S.; Izquierdo, Luis Glycobiology, Vol. 18, Issue 5, p. 367-383 https://doi.org/10.1093/glycob/cwn014	journal	February 2008
Molecular cloning and enzymatic characterization of a Trichoderma reesei 1,2-α-d-mannosidase Maras, Marleen; Callewaert, Nico; Piens, Kathleen Journal of Biotechnology, Vol. 77, Issue 2-3, p. 255-263 https://doi.org/10.1016/S0168-1656(99)00222-9	journal	February 2000
The effects of culture conditions on the glycosylation of secreted human placental alkaline phosphatase produced in Chinese hamster ovary cells Nam, Jong Hyun; Zhang, Fuming; Ermonval, Myriam Biotechnology and Bioengineering, Vol. 100, Issue 6, p. 1178-1192 https://doi.org/10.1002/bit.21853	journal	August 2008
Heterologous protein expression in filamentous fungi Nevalainen, K. M. Helena; Te'o, Valentino S. J.; Bergquist, Peter L. Trends in Biotechnology, Vol. 23, Issue 9, p. 468-474 https://doi.org/10.1016/j.tibtech.2005.06.002	journal	September 2005
Aspergillus oryzae laeA Regulates Kojic Acid Synthesis Genes Oda, Ken; Kobayashi, Akiko; Ohashi, Shinichi Bioscience, Biotechnology, and Biochemistry, Vol. 75, Issue 9, p. 1832-1834 https://doi.org/10.1271/bbb.110235	journal	September 2011
Human Sperm Binding Is Mediated by the Sialyl-Lewisx Oligosaccharide on the Zona Pellucida Pang, P.-C.; Chiu, P. C. N.; Lee, C.-L. Science, Vol. 333, Issue 6050, p. 1761-1764 https://doi.org/10.1126/science.1207438	journal	August 2011
Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88 Pel, Herman J.; de Winde, Johannes H.; Archer, David B. Nature Biotechnology, Vol. 25, Issue 2, p. 221-231 https://doi.org/10.1038/nbt1282	journal	January 2007
veA-dependent RNA-pol II transcription elongation factor-like protein, RtfA, is associated with secondary metabolism and morphological development in Aspergillus nidulans Ramamoorthy, Vellaisamy; Shantappa, Sourabha; Dhingra, Sourabh Molecular Microbiology, Vol. 85, Issue 4, p. 795-814 https://doi.org/10.1111/j.1365-2958.2012.08142.x	journal	July 2012
Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans Reyes-Dominguez, Yazmid; Bok, Jin Woo; Berger, Harald Molecular Microbiology, Vol. 76, Issue 6, p. 1376-1386 https://doi.org/10.1111/j.1365-2958.2010.07051.x	journal	February 2010
Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism Roze, Ludmila V.; Chanda, Anindya; Laivenieks, Maris BMC Biochemistry, Vol. 11, Issue 1, Article No. 33 https://doi.org/10.1186/1471-2091-11-33	journal	January 2010
Heterologous expression system in Aspergillus oryzae for fungal biosynthetic gene clusters of secondary metabolites Sakai, Kanae; Kinoshita, Hiroshi; Nihira, Takuya Applied Microbiology and Biotechnology, Vol. 93, Issue 5, p. 2011-2022 https://doi.org/10.1007/s00253-011-3657-9	journal	November 2011
Microbial production of organic acids: expanding the markets Sauer, Michael; Porro, Danilo; Mattanovich, Diethard Trends in Biotechnology, Vol. 26, Issue 2, p. 100-108 https://doi.org/10.1016/j.tibtech.2007.11.006	journal	February 2008
Organic Acid Production by Filamentous Fungi Magnuson, Jon K.; Lasure, Linda L.; Tkacz, Jan S. Advances in Fungal Biotechnology for Industry, Agriculture, and Medicine, p. 307-340 https://doi.org/10.1007/978-1-4419-8859-1_12	book	January 2004
CDG-Id caused by homozygosity for an ALG3 mutation due to segmental maternal isodisomy UPD3(q21.3-qter) Schollen, E.; Grünewald, S.; Keldermans, L. European Journal of Medical Genetics, Vol. 48, Issue 2, p. 153-158 https://doi.org/10.1016/j.ejmg.2005.01.002	journal	April 2005
On the safety of Aspergillus niger - a review Schuster, E.; Dunn-Coleman, N.; Frisvad, J. Applied Microbiology and Biotechnology, Vol. 59, Issue 4-5, p. 426-435 https://doi.org/10.1007/s00253-002-1032-6	journal	January 2002
Melamine Deaminase and Atrazine Chlorohydrolase: 98 Percent Identical but Functionally Different Seffernick, J. L.; de Souza, M. L.; Sadowsky, M. J. Journal of Bacteriology, Vol. 183, Issue 8, p. 2405-2410 https://doi.org/10.1128/JB.183.8.2405-2410.2001	journal	April 2001
Overexpression of the Aspergillus nidulans histone 4 acetyltransferase EsaA increases activation of secondary metabolite production Soukup, Alexandra A.; Chiang, Yi-Ming; Bok, Jin Woo Molecular Microbiology, Vol. 86, Issue 2, p. 314-330 https://doi.org/10.1111/j.1365-2958.2012.08195.x	journal	August 2012
The ARO4 gene of Candida albicans encodes a tyrosine-sensitive DAHP synthase: evolution, functional conservation and phenotype of Aro3p-, Aro4p-deficient mutants Livi, George P.; McLaughlin, Megan M.; Sousa, Silvino Microbiology, Vol. 148, Issue 5, p. 1291-1303 https://doi.org/10.1099/00221287-148-5-1291	journal	May 2002
Carbohydrate-Deficient Glycoprotein Syndrome - A Fourth Subtype Stibler, Helena; Stephani, U.; Kutsch, Ulrike Neuropediatrics, Vol. 26, Issue 05, p. 235-237 https://doi.org/10.1055/s-2007-979762	journal	October 1995
Congenital Disorder of Glycosylation Id Presenting with Hyperinsulinemic Hypoglycemia and Islet Cell Hyperplasia Sun, Liangwu; Eklund, Erik A.; Chung, Wendy K. The Journal of Clinical Endocrinology & Metabolism, Vol. 90, Issue 7, p. 4371-4375 https://doi.org/10.1210/jc.2005-0250	journal	July 2005
Quality Control and Protein Folding in the Secretory Pathway Trombetta, E. Sergio; Parodi, Armando J. Annual Review of Cell and Developmental Biology, Vol. 19, Issue 1, p. 649-676 https://doi.org/10.1146/annurev.cellbio.19.110701.153949	journal	November 2003
Analytical and computational approaches to define the Aspergillus niger secretome Tsang, Adrian; Butler, Gregory; Powlowski, Justin Fungal Genetics and Biology, Vol. 46, Issue 1, p. S153-S160 https://doi.org/10.1016/j.fgb.2008.07.014	journal	March 2009
Conversion of a β-Ketoacyl Synthase to a Malonyl Decarboxylase by Replacement of the Active-Site Cysteine with Glutamine Witkowski, Andrzej; Joshi, Anil K.; Lindqvist, Ylva Biochemistry, Vol. 38, Issue 36, p. 11643-11650 https://doi.org/10.1021/bi990993h	journal	September 1999
Molecular cloning and characterization of the global regulator LaeA in Penicillium citrinum Xing, Wei; Deng, Chao; Hu, Chang-Hua Biotechnology Letters, Vol. 32, Issue 11, p. 1733-1737 https://doi.org/10.1007/s10529-010-0375-9	journal	August 2010
Unraveling the Mechanism of Protein N-Glycosylation Yan, Aixin; Lennarz, William J. Journal of Biological Chemistry, Vol. 280, Issue 5, p. 3121-3124 https://doi.org/10.1074/jbc.R400036200	journal	December 2004
Global analysis of gene transcription regulation in prokaryotes Zhou, D.; Yang, R. Cellular and Molecular Life Sciences, Vol. 63, Issue 19-20, p. 2260-2290 https://doi.org/10.1007/s00018-006-6184-6	journal	August 2006

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