Mycotoxin-free Aspergillus oryzae strain lineage for alternative and novel protein production at industrial scale.
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| Title: | Mycotoxin-free Aspergillus oryzae strain lineage for alternative and novel protein production at industrial scale. |
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| Authors: | Lehmbeck, Jan1 (AUTHOR), Andersen, Birgitte1 (AUTHOR), Sáez-Sáez, Javier1 (AUTHOR), Frisvad, Jens Christian2 (AUTHOR), Arnau, José1 (AUTHOR) j.arnau@21st.bio |
| Source: | Applied Microbiology & Biotechnology. 4/11/2025, Vol. 109 Issue 1, p1-10. 10p. |
| Subjects: | Koji, Recombinant proteins, Penicillin G, Life sciences, Cytology, Aspergillus flavus |
| Abstract: | Advanced industrial strains of Aspergillus oryzae have been used for decades for the production of recombinant proteins including food and feed enzymes at large scale. The A. oryzae strain lineage evaluated in this review derives from the proprietary Novozymes (now Novonesis) strain collection. A. oryzae wild-type strains have the potential to produce three different mycotoxins (aflatoxins (AFL), cyclopiazonic acid (CPA), and 3-nitropropionic acid (3-NPA)). Here, we review the work originally performed at Novozymes to identify a strain (BECh1) that contained a large chromosomal deletion comprising both AFL and CPA gene clusters, significantly improving the safety of the lineage. The description of the deleted region is presented here. As the genetic basis for 3-NPA biosynthesis was recently revealed, we describe here that this A. oryzae lineage contains an additional large deletion that encompasses the 3-NPA biosynthetic genes npaA and npaB, thereby rendering the strains unable to produce any mycotoxin. Further strain development has resulted in strains devoid of penicillin production by inactivation of the penicillin G gene cluster (penG). This strain lineage represents the first example of mycotoxin-free A. oryzae for production of recombinant (alternative) novel food proteins. Recently, bovine beta-lactoglobulin made using a strain of this lineage has received GRAS status and can be commercialized for use in food in the USA. With its history of safe use in food and feed, the lack of toxigenic potential and the ability to differentiate strains with modern technologies, this A. oryzae strain can be considered safe as other organisms with a Quality Presumption of Safety (QPS) status in Europe. QPS is not applicable to filamentous fungi and only granted at the species level to bacteria and a few yeast species. We suggest modernizing the QPS concept to become strain rather than species specific and present arguments to qualify this strain lineage as QPS or QPS-like. Key points: • The biosynthetic genes for 3-nitropropionic acid have been recently characterized. • An industrial strain lineage for food protein production lacks all known mycotoxin genes. • Proteins produced in this mycotoxin-free lineage should entail lower regulatory requirements. [ABSTRACT FROM AUTHOR] |
| Copyright of Applied Microbiology & Biotechnology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
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| Header | DbId: egs DbLabel: Engineering Source An: 184452916 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Mycotoxin-free Aspergillus oryzae strain lineage for alternative and novel protein production at industrial scale. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Lehmbeck%2C+Jan%22">Lehmbeck, Jan</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Andersen%2C+Birgitte%22">Andersen, Birgitte</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sáez-Sáez%2C+Javier%22">Sáez-Sáez, Javier</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Frisvad%2C+Jens+Christian%22">Frisvad, Jens Christian</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Arnau%2C+José%22">Arnau, José</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> j.arnau@21st.bio</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Applied+Microbiology+%26+Biotechnology%22">Applied Microbiology & Biotechnology</searchLink>. 4/11/2025, Vol. 109 Issue 1, p1-10. 10p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Koji%22">Koji</searchLink><br /><searchLink fieldCode="DE" term="%22Recombinant+proteins%22">Recombinant proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Penicillin+G%22">Penicillin G</searchLink><br /><searchLink fieldCode="DE" term="%22Life+sciences%22">Life sciences</searchLink><br /><searchLink fieldCode="DE" term="%22Cytology%22">Cytology</searchLink><br /><searchLink fieldCode="DE" term="%22Aspergillus+flavus%22">Aspergillus flavus</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Advanced industrial strains of Aspergillus oryzae have been used for decades for the production of recombinant proteins including food and feed enzymes at large scale. The A. oryzae strain lineage evaluated in this review derives from the proprietary Novozymes (now Novonesis) strain collection. A. oryzae wild-type strains have the potential to produce three different mycotoxins (aflatoxins (AFL), cyclopiazonic acid (CPA), and 3-nitropropionic acid (3-NPA)). Here, we review the work originally performed at Novozymes to identify a strain (BECh1) that contained a large chromosomal deletion comprising both AFL and CPA gene clusters, significantly improving the safety of the lineage. The description of the deleted region is presented here. As the genetic basis for 3-NPA biosynthesis was recently revealed, we describe here that this A. oryzae lineage contains an additional large deletion that encompasses the 3-NPA biosynthetic genes npaA and npaB, thereby rendering the strains unable to produce any mycotoxin. Further strain development has resulted in strains devoid of penicillin production by inactivation of the penicillin G gene cluster (penG). This strain lineage represents the first example of mycotoxin-free A. oryzae for production of recombinant (alternative) novel food proteins. Recently, bovine beta-lactoglobulin made using a strain of this lineage has received GRAS status and can be commercialized for use in food in the USA. With its history of safe use in food and feed, the lack of toxigenic potential and the ability to differentiate strains with modern technologies, this A. oryzae strain can be considered safe as other organisms with a Quality Presumption of Safety (QPS) status in Europe. QPS is not applicable to filamentous fungi and only granted at the species level to bacteria and a few yeast species. We suggest modernizing the QPS concept to become strain rather than species specific and present arguments to qualify this strain lineage as QPS or QPS-like. Key points: • The biosynthetic genes for 3-nitropropionic acid have been recently characterized. • An industrial strain lineage for food protein production lacks all known mycotoxin genes. • Proteins produced in this mycotoxin-free lineage should entail lower regulatory requirements. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Applied Microbiology & Biotechnology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1007/s00253-025-13482-6 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 10 StartPage: 1 Subjects: – SubjectFull: Koji Type: general – SubjectFull: Recombinant proteins Type: general – SubjectFull: Penicillin G Type: general – SubjectFull: Life sciences Type: general – SubjectFull: Cytology Type: general – SubjectFull: Aspergillus flavus Type: general Titles: – TitleFull: Mycotoxin-free Aspergillus oryzae strain lineage for alternative and novel protein production at industrial scale. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Lehmbeck, Jan – PersonEntity: Name: NameFull: Andersen, Birgitte – PersonEntity: Name: NameFull: Sáez-Sáez, Javier – PersonEntity: Name: NameFull: Frisvad, Jens Christian – PersonEntity: Name: NameFull: Arnau, José IsPartOfRelationships: – BibEntity: Dates: – D: 11 M: 04 Text: 4/11/2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 01757598 Numbering: – Type: volume Value: 109 – Type: issue Value: 1 Titles: – TitleFull: Applied Microbiology & Biotechnology Type: main |
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