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Characterization of the P450 Monooxygenase LobP1 as C-32 Hydroxylase in Lobophorin Biosynthesis
  • +6
  • Bin Tan,
  • Qingbo Zhang,
  • Ji Xiao,
  • Cheng-shan Yuan,
  • Yuchan Chen,
  • Siqiang Chen,
  • Weimin Zhang,
  • Yiguang Zhu,
  • Changsheng Zhang
Bin Tan
SCSIO CAS
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Qingbo Zhang
South China Sea Institute of Oceanology Chinese Academy of Sciences
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Ji Xiao
South China Sea Institute of Oceanology Chinese Academy of Sciences
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Cheng-shan Yuan
South China Sea Institute of Oceanology Chinese Academy of Sciences
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Yuchan Chen
Institute of Microbiology, Guangdong Academy of Sciences
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Siqiang Chen
South China Sea Institute of Oceanology Chinese Academy of Sciences
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Weimin Zhang
Guangdong Institute of Microbiology
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Yiguang Zhu
South China Sea Institute of Oceanology Chinese Academy of Sciences
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Changsheng Zhang
South China Sea Institute of Oceanology Chinese Academy of Sciences

Corresponding Author:czhang@scsio.ac.cn

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Abstract

Lobophorins (LOBs) belong to a large family of spirotetronate antibiotics with antibacterial and antitumor activities. In this study, we demonstrated the function of LobP1, a P450 monooxygenase encoded in the LOB biosynthetic gene cluster, by in vivo deletion and in vitro biochemical assays. The disruption of lobP1 led to the isolation of three new LOBs derivatives (3‒5) and three known ones (6‒8) without the hydroxyl group at C-32. LobP1 was shown to have relatively broad substrate scope. Determing the kinetic parameters of LobP1 towards different substrates revealed that LobP1 preferred substrate with a nitrosugar. The major product LOB E (6) from the ∆lobP1 mutant displayed better cytotoxic activities against several cancer cell lines than LOB B, the C-32 hydroxlated counterpart.
12 Jan 20231st Revision Received
13 Jan 2023Submission Checks Completed
13 Jan 2023Assigned to Editor
13 Jan 2023Review(s) Completed, Editorial Evaluation Pending
13 Jan 2023Editorial Decision: Accept