Pyridoxal-5′-phosphate-dependent enzyme GenB3 Catalyzes C-3′,4′-dideoxygenation in gentamicin biosynthesis.
| Title: | Pyridoxal-5′-phosphate-dependent enzyme GenB3 Catalyzes C-3′,4′-dideoxygenation in gentamicin biosynthesis. |
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| Authors: | Zhou, Shaotong1 (AUTHOR), Chen, Xiaotang1 (AUTHOR), Ni, Xianpu1 (AUTHOR) nixianpu126@126.com, Liu, Yu1 (AUTHOR), Zhang, Hui1 (AUTHOR), Dong, Min2 (AUTHOR) mindong@tju.edu.cn, Xia, Huanzhang1 (AUTHOR) hzxia@syphu.edu.cn |
| Source: | Microbial Cell Factories. 3/9/2021, Vol. 20 Issue 1, p1-12. 12p. |
| Subject Terms: | *GENTAMICIN, *BIOSYNTHESIS, *ENZYMES, *PHOSPHORYLATION |
| Abstract: | Background: The C-3′,4′-dideoxygenation structure in gentamicin can prevent deactivation by aminoglycoside 3′-phosphotransferase (APH(3′)) in drug-resistant pathogens. However, the enzyme catalyzing the dideoxygenation step in the gentamicin biosynthesis pathway remains unknown. Results: Here, we report that GenP catalyzes 3′ phosphorylation of the gentamicin biosynthesis intermediates JI-20A, JI-20Ba, and JI-20B. We further demonstrate that the pyridoxal-5′-phosphate (PLP)-dependent enzyme GenB3 uses these phosphorylated substrates to form 3′,4′-dideoxy-4′,5′-ene-6′-oxo products. The following C-6′-transamination and the GenB4-catalyzed reduction of 4′,5′-olefin lead to the formation of gentamicin C. To the best of our knowledge, GenB3 is the first PLP-dependent enzyme catalyzing dideoxygenation in aminoglycoside biosynthesis. Conclusions: This discovery solves a long-standing puzzle in gentamicin biosynthesis and enriches our knowledge of the chemistry of PLP-dependent enzymes. Interestingly, these results demonstrate that to evade APH(3′) deactivation by pathogens, the gentamicin producers evolved a smart strategy, which utilized their own APH(3′) to activate hydroxyls as leaving groups for the 3′,4′-dideoxygenation in gentamicin biosynthesis. [ABSTRACT FROM AUTHOR] |
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| Items | – Name: Title Label: Title Group: Ti Data: Pyridoxal-5′-phosphate-dependent enzyme GenB3 Catalyzes C-3′,4′-dideoxygenation in gentamicin biosynthesis. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Zhou%2C+Shaotong%22">Zhou, Shaotong</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Xiaotang%22">Chen, Xiaotang</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ni%2C+Xianpu%22">Ni, Xianpu</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> nixianpu126@126.com</i><br /><searchLink fieldCode="AR" term="%22Liu%2C+Yu%22">Liu, Yu</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Hui%22">Zhang, Hui</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dong%2C+Min%22">Dong, Min</searchLink><relatesTo>2</relatesTo> (AUTHOR)<i> mindong@tju.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Xia%2C+Huanzhang%22">Xia, Huanzhang</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> hzxia@syphu.edu.cn</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Microbial+Cell+Factories%22">Microbial Cell Factories</searchLink>. 3/9/2021, Vol. 20 Issue 1, p1-12. 12p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22GENTAMICIN%22">GENTAMICIN</searchLink><br />*<searchLink fieldCode="DE" term="%22BIOSYNTHESIS%22">BIOSYNTHESIS</searchLink><br />*<searchLink fieldCode="DE" term="%22ENZYMES%22">ENZYMES</searchLink><br />*<searchLink fieldCode="DE" term="%22PHOSPHORYLATION%22">PHOSPHORYLATION</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Background: The C-3′,4′-dideoxygenation structure in gentamicin can prevent deactivation by aminoglycoside 3′-phosphotransferase (APH(3′)) in drug-resistant pathogens. However, the enzyme catalyzing the dideoxygenation step in the gentamicin biosynthesis pathway remains unknown. Results: Here, we report that GenP catalyzes 3′ phosphorylation of the gentamicin biosynthesis intermediates JI-20A, JI-20Ba, and JI-20B. We further demonstrate that the pyridoxal-5′-phosphate (PLP)-dependent enzyme GenB3 uses these phosphorylated substrates to form 3′,4′-dideoxy-4′,5′-ene-6′-oxo products. The following C-6′-transamination and the GenB4-catalyzed reduction of 4′,5′-olefin lead to the formation of gentamicin C. To the best of our knowledge, GenB3 is the first PLP-dependent enzyme catalyzing dideoxygenation in aminoglycoside biosynthesis. Conclusions: This discovery solves a long-standing puzzle in gentamicin biosynthesis and enriches our knowledge of the chemistry of PLP-dependent enzymes. Interestingly, these results demonstrate that to evade APH(3′) deactivation by pathogens, the gentamicin producers evolved a smart strategy, which utilized their own APH(3′) to activate hydroxyls as leaving groups for the 3′,4′-dideoxygenation in gentamicin biosynthesis. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Microbial Cell Factories is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. 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: 10.1186/s12934-021-01558-7 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 1 Subjects: – SubjectFull: GENTAMICIN Type: general – SubjectFull: BIOSYNTHESIS Type: general – SubjectFull: ENZYMES Type: general – SubjectFull: PHOSPHORYLATION Type: general Titles: – TitleFull: Pyridoxal-5′-phosphate-dependent enzyme GenB3 Catalyzes C-3′,4′-dideoxygenation in gentamicin biosynthesis. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Zhou, Shaotong – PersonEntity: Name: NameFull: Chen, Xiaotang – PersonEntity: Name: NameFull: Ni, Xianpu – PersonEntity: Name: NameFull: Liu, Yu – PersonEntity: Name: NameFull: Zhang, Hui – PersonEntity: Name: NameFull: Dong, Min – PersonEntity: Name: NameFull: Xia, Huanzhang IsPartOfRelationships: – BibEntity: Dates: – D: 09 M: 03 Text: 3/9/2021 Type: published Y: 2021 Identifiers: – Type: issn-print Value: 14752859 Numbering: – Type: volume Value: 20 – Type: issue Value: 1 Titles: – TitleFull: Microbial Cell Factories Type: main |
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