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Efficient production of a cyclic dipeptide (cyclo-TA) using heterologous expression system of filamentous fungus Aspergillus oryzae

BACKGROUND: Cyclic dipeptides are an important class of natural products owing to their structural diversity and biological activities. In fungi, the cyclo-ring system is formed through the condensation of two α-amino acids via non-ribosomal peptide synthetase (NRPS). However, there are few investig...

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Autores principales: Qi, Jianzhao, Han, Haiyan, Sui, Dan, Tan, Shengnan, Liu, Changli, Wang, Pengchao, Xie, Chunliang, Xia, Xuekui, Gao, Jin-ming, Liu, Chengwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290255/
https://www.ncbi.nlm.nih.gov/pubmed/35843946
http://dx.doi.org/10.1186/s12934-022-01872-8
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author Qi, Jianzhao
Han, Haiyan
Sui, Dan
Tan, Shengnan
Liu, Changli
Wang, Pengchao
Xie, Chunliang
Xia, Xuekui
Gao, Jin-ming
Liu, Chengwei
author_facet Qi, Jianzhao
Han, Haiyan
Sui, Dan
Tan, Shengnan
Liu, Changli
Wang, Pengchao
Xie, Chunliang
Xia, Xuekui
Gao, Jin-ming
Liu, Chengwei
author_sort Qi, Jianzhao
collection PubMed
description BACKGROUND: Cyclic dipeptides are an important class of natural products owing to their structural diversity and biological activities. In fungi, the cyclo-ring system is formed through the condensation of two α-amino acids via non-ribosomal peptide synthetase (NRPS). However, there are few investigations on the functional identification of this enzyme. Additionally, information on how to increase the production of cyclic dipeptide molecules is relatively scarce. RESULTS: We isolated the Eurotium cristatum NWAFU-1 fungus from Jing-Wei Fu brick tea, whose fermentation metabolites contain echinulin-related cyclic dipeptide molecules. We cloned the cirC gene, encoding an NRPS, from E. Cristatum NWAFU-1 and transferred it into the heterologous host Aspergillus oryzae. This transformant produced a novel metabolite possessing an l-tryptophan-l-alanine cyclic dipeptide backbone (Cyclo-TA). Based on the results of heterologous expression and microsomal catalysis, CriC is the first NRPS characterized in fungi that catalyzes the formation of a cyclic dipeptide from l-tryptophan and l-alanine. After substrate feeding, the final yield reached 34 mg/L. In this study, we have characterized a novel NRPS and developed a new method for cyclic dipeptide production. CONCLUSIONS: In this study we successfully expressed the E. Cristatum NWAFU-1 criC gene in A. oryzae to efficiently produce cyclic dipeptide compounds. Our findings indicate that the A. oryzae heterologous expression system constitutes an efficient method for the biosynthesis of fungal Cyclic dipeptides. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12934-022-01872-8.
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spelling pubmed-92902552022-07-19 Efficient production of a cyclic dipeptide (cyclo-TA) using heterologous expression system of filamentous fungus Aspergillus oryzae Qi, Jianzhao Han, Haiyan Sui, Dan Tan, Shengnan Liu, Changli Wang, Pengchao Xie, Chunliang Xia, Xuekui Gao, Jin-ming Liu, Chengwei Microb Cell Fact Research BACKGROUND: Cyclic dipeptides are an important class of natural products owing to their structural diversity and biological activities. In fungi, the cyclo-ring system is formed through the condensation of two α-amino acids via non-ribosomal peptide synthetase (NRPS). However, there are few investigations on the functional identification of this enzyme. Additionally, information on how to increase the production of cyclic dipeptide molecules is relatively scarce. RESULTS: We isolated the Eurotium cristatum NWAFU-1 fungus from Jing-Wei Fu brick tea, whose fermentation metabolites contain echinulin-related cyclic dipeptide molecules. We cloned the cirC gene, encoding an NRPS, from E. Cristatum NWAFU-1 and transferred it into the heterologous host Aspergillus oryzae. This transformant produced a novel metabolite possessing an l-tryptophan-l-alanine cyclic dipeptide backbone (Cyclo-TA). Based on the results of heterologous expression and microsomal catalysis, CriC is the first NRPS characterized in fungi that catalyzes the formation of a cyclic dipeptide from l-tryptophan and l-alanine. After substrate feeding, the final yield reached 34 mg/L. In this study, we have characterized a novel NRPS and developed a new method for cyclic dipeptide production. CONCLUSIONS: In this study we successfully expressed the E. Cristatum NWAFU-1 criC gene in A. oryzae to efficiently produce cyclic dipeptide compounds. Our findings indicate that the A. oryzae heterologous expression system constitutes an efficient method for the biosynthesis of fungal Cyclic dipeptides. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12934-022-01872-8. BioMed Central 2022-07-18 /pmc/articles/PMC9290255/ /pubmed/35843946 http://dx.doi.org/10.1186/s12934-022-01872-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Qi, Jianzhao
Han, Haiyan
Sui, Dan
Tan, Shengnan
Liu, Changli
Wang, Pengchao
Xie, Chunliang
Xia, Xuekui
Gao, Jin-ming
Liu, Chengwei
Efficient production of a cyclic dipeptide (cyclo-TA) using heterologous expression system of filamentous fungus Aspergillus oryzae
title Efficient production of a cyclic dipeptide (cyclo-TA) using heterologous expression system of filamentous fungus Aspergillus oryzae
title_full Efficient production of a cyclic dipeptide (cyclo-TA) using heterologous expression system of filamentous fungus Aspergillus oryzae
title_fullStr Efficient production of a cyclic dipeptide (cyclo-TA) using heterologous expression system of filamentous fungus Aspergillus oryzae
title_full_unstemmed Efficient production of a cyclic dipeptide (cyclo-TA) using heterologous expression system of filamentous fungus Aspergillus oryzae
title_short Efficient production of a cyclic dipeptide (cyclo-TA) using heterologous expression system of filamentous fungus Aspergillus oryzae
title_sort efficient production of a cyclic dipeptide (cyclo-ta) using heterologous expression system of filamentous fungus aspergillus oryzae
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290255/
https://www.ncbi.nlm.nih.gov/pubmed/35843946
http://dx.doi.org/10.1186/s12934-022-01872-8
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