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β-Hydroxylation of α-amino-β-hydroxylbutanoyl-glycyluridine catalyzed by a nonheme hydroxylase ensures the maturation of caprazamycin

Caprazamycin is a nucleoside antibiotic that inhibits phospho-N-acetylmuramyl-pentapeptide translocase (MraY). The biosynthesis of nucleoside antibiotics has been studied but is still far from completion. The present study characterized enzymes Cpz10, Cpz15, Cpz27, Mur17, Mur23 out of caprazamycin/m...

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Autores principales: Zadeh, Saeid Malek, Chen, Mei-Hua, Wang, Zhe-Chong, Astani, Elahe K., Lo, I-Wen, Lin, Kuan-Hung, Hsu, Ning-Shian, Adhikari, Kamal, Lyu, Syue-Yi, Tsai, Hsin-Ying, Terasawa, Yuma, Yabe, Miyuki, Yamamoto, Kazuki, Ichikawa, Satoshi, Li, Tsung-Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814697/
https://www.ncbi.nlm.nih.gov/pubmed/36697788
http://dx.doi.org/10.1038/s42004-022-00703-6
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author Zadeh, Saeid Malek
Chen, Mei-Hua
Wang, Zhe-Chong
Astani, Elahe K.
Lo, I-Wen
Lin, Kuan-Hung
Hsu, Ning-Shian
Adhikari, Kamal
Lyu, Syue-Yi
Tsai, Hsin-Ying
Terasawa, Yuma
Yabe, Miyuki
Yamamoto, Kazuki
Ichikawa, Satoshi
Li, Tsung-Lin
author_facet Zadeh, Saeid Malek
Chen, Mei-Hua
Wang, Zhe-Chong
Astani, Elahe K.
Lo, I-Wen
Lin, Kuan-Hung
Hsu, Ning-Shian
Adhikari, Kamal
Lyu, Syue-Yi
Tsai, Hsin-Ying
Terasawa, Yuma
Yabe, Miyuki
Yamamoto, Kazuki
Ichikawa, Satoshi
Li, Tsung-Lin
author_sort Zadeh, Saeid Malek
collection PubMed
description Caprazamycin is a nucleoside antibiotic that inhibits phospho-N-acetylmuramyl-pentapeptide translocase (MraY). The biosynthesis of nucleoside antibiotics has been studied but is still far from completion. The present study characterized enzymes Cpz10, Cpz15, Cpz27, Mur17, Mur23 out of caprazamycin/muraymycin biosynthetic gene cluster, particularly the nonheme αKG-dependent enzyme Cpz10. Cpz15 is a β-hydroxylase converting uridine mono-phosphate to uridine 5′ aldehyde, then incorporating with threonine by Mur17 (Cpz14) to form 5′-C-glycyluridine. Cpz10 hydroxylates synthetic 11 to 12 in vitro. Major product 13 derived from mutant Δcpz10 is phosphorylated by Cpz27. β-Hydroxylation of 11 by Cpz10 permits the maturation of caprazamycin, but decarboxylation of 11 by Mur23 oriented to muraymycin formation. Cpz10 recruits two iron atoms to activate dioxygen with regio-/stereo-specificity and commit electron/charge transfer, respectively. The chemo-physical interrogations should greatly advance our understanding of caprazamycin biosynthesis, which is conducive to pathway/protein engineering for developing more effective nucleoside antibiotics.
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spelling pubmed-98146972023-01-10 β-Hydroxylation of α-amino-β-hydroxylbutanoyl-glycyluridine catalyzed by a nonheme hydroxylase ensures the maturation of caprazamycin Zadeh, Saeid Malek Chen, Mei-Hua Wang, Zhe-Chong Astani, Elahe K. Lo, I-Wen Lin, Kuan-Hung Hsu, Ning-Shian Adhikari, Kamal Lyu, Syue-Yi Tsai, Hsin-Ying Terasawa, Yuma Yabe, Miyuki Yamamoto, Kazuki Ichikawa, Satoshi Li, Tsung-Lin Commun Chem Article Caprazamycin is a nucleoside antibiotic that inhibits phospho-N-acetylmuramyl-pentapeptide translocase (MraY). The biosynthesis of nucleoside antibiotics has been studied but is still far from completion. The present study characterized enzymes Cpz10, Cpz15, Cpz27, Mur17, Mur23 out of caprazamycin/muraymycin biosynthetic gene cluster, particularly the nonheme αKG-dependent enzyme Cpz10. Cpz15 is a β-hydroxylase converting uridine mono-phosphate to uridine 5′ aldehyde, then incorporating with threonine by Mur17 (Cpz14) to form 5′-C-glycyluridine. Cpz10 hydroxylates synthetic 11 to 12 in vitro. Major product 13 derived from mutant Δcpz10 is phosphorylated by Cpz27. β-Hydroxylation of 11 by Cpz10 permits the maturation of caprazamycin, but decarboxylation of 11 by Mur23 oriented to muraymycin formation. Cpz10 recruits two iron atoms to activate dioxygen with regio-/stereo-specificity and commit electron/charge transfer, respectively. The chemo-physical interrogations should greatly advance our understanding of caprazamycin biosynthesis, which is conducive to pathway/protein engineering for developing more effective nucleoside antibiotics. Nature Publishing Group UK 2022-07-28 /pmc/articles/PMC9814697/ /pubmed/36697788 http://dx.doi.org/10.1038/s42004-022-00703-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zadeh, Saeid Malek
Chen, Mei-Hua
Wang, Zhe-Chong
Astani, Elahe K.
Lo, I-Wen
Lin, Kuan-Hung
Hsu, Ning-Shian
Adhikari, Kamal
Lyu, Syue-Yi
Tsai, Hsin-Ying
Terasawa, Yuma
Yabe, Miyuki
Yamamoto, Kazuki
Ichikawa, Satoshi
Li, Tsung-Lin
β-Hydroxylation of α-amino-β-hydroxylbutanoyl-glycyluridine catalyzed by a nonheme hydroxylase ensures the maturation of caprazamycin
title β-Hydroxylation of α-amino-β-hydroxylbutanoyl-glycyluridine catalyzed by a nonheme hydroxylase ensures the maturation of caprazamycin
title_full β-Hydroxylation of α-amino-β-hydroxylbutanoyl-glycyluridine catalyzed by a nonheme hydroxylase ensures the maturation of caprazamycin
title_fullStr β-Hydroxylation of α-amino-β-hydroxylbutanoyl-glycyluridine catalyzed by a nonheme hydroxylase ensures the maturation of caprazamycin
title_full_unstemmed β-Hydroxylation of α-amino-β-hydroxylbutanoyl-glycyluridine catalyzed by a nonheme hydroxylase ensures the maturation of caprazamycin
title_short β-Hydroxylation of α-amino-β-hydroxylbutanoyl-glycyluridine catalyzed by a nonheme hydroxylase ensures the maturation of caprazamycin
title_sort β-hydroxylation of α-amino-β-hydroxylbutanoyl-glycyluridine catalyzed by a nonheme hydroxylase ensures the maturation of caprazamycin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814697/
https://www.ncbi.nlm.nih.gov/pubmed/36697788
http://dx.doi.org/10.1038/s42004-022-00703-6
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