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New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum
Chaetoglobosin A is a complex macrocyclic alkaloid with potent antimycotic, antiparasitic and antitumor properties. However, the low output and high cost of chaetoglobosin A biosynthesis have hampered the application and commercialization of chaetoglobosin A in agriculture and biomedicine. Here, the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9518988/ https://www.ncbi.nlm.nih.gov/pubmed/35930651 http://dx.doi.org/10.1111/1751-7915.14111 |
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author | Zhao, Shanshan Lin, Congyu Cheng, Ming Zhang, Kai Wang, Zhengran Zhao, Tong Yang, Qian |
author_facet | Zhao, Shanshan Lin, Congyu Cheng, Ming Zhang, Kai Wang, Zhengran Zhao, Tong Yang, Qian |
author_sort | Zhao, Shanshan |
collection | PubMed |
description | Chaetoglobosin A is a complex macrocyclic alkaloid with potent antimycotic, antiparasitic and antitumor properties. However, the low output and high cost of chaetoglobosin A biosynthesis have hampered the application and commercialization of chaetoglobosin A in agriculture and biomedicine. Here, the CgMfs1 gene, which encodes the major facilitator superfamily secondary transporter, was identified based on bioinformatics analysis, and an intensive study of its effects on chaetoglobosin A biosynthesis and secretion was performed using CgMfs1‐silencing and CgMfs1‐overexpression strategies. Inactivation of CgMfs1 caused a notable decrease in chaetoglobosin A yield from 58.66 mg/L to 19.95 mg/L (MFS1–3) and 17.13 mg/L (MFS1–4). The use of an efficient expression plasmid in Chaetomium globosum W7 to generate the overexpression mutant OEX13 resulted in the highest chaetoglobosin A increase to 298.77 mg/L. Interestingly, the transcription level of the polyketide synthase gene significantly fluctuated with the change in CgMfs1, confirming that the predicted efflux gene CgMfs1 could play a crucial role in chaetoglobosin A transportation. Effective efflux of chaetoglobosin A could possibly alleviate feedback inhibition, resulting in notable increase in the expression of the polyketide synthase gene. Furthermore, we utilized cornstalk as the fermentation substrate to produce chaetoglobosin A, and scanning electron microscopy and Fourier transform‐infrared spectroscopy revealed that the strain OEX13 could well degrade cornstalk, presenting significant increases in the chaetoglobosin A yield, when compared with that produced by the wild‐type strain (from 40.32 to 191.90 mg/L). Thus, this research provides a novel analogous engineering strategy for the construction of high‐yielding strain and offers new insight into large‐scale chaetoglobosin A production. |
format | Online Article Text |
id | pubmed-9518988 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95189882022-10-05 New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum Zhao, Shanshan Lin, Congyu Cheng, Ming Zhang, Kai Wang, Zhengran Zhao, Tong Yang, Qian Microb Biotechnol Research Articles Chaetoglobosin A is a complex macrocyclic alkaloid with potent antimycotic, antiparasitic and antitumor properties. However, the low output and high cost of chaetoglobosin A biosynthesis have hampered the application and commercialization of chaetoglobosin A in agriculture and biomedicine. Here, the CgMfs1 gene, which encodes the major facilitator superfamily secondary transporter, was identified based on bioinformatics analysis, and an intensive study of its effects on chaetoglobosin A biosynthesis and secretion was performed using CgMfs1‐silencing and CgMfs1‐overexpression strategies. Inactivation of CgMfs1 caused a notable decrease in chaetoglobosin A yield from 58.66 mg/L to 19.95 mg/L (MFS1–3) and 17.13 mg/L (MFS1–4). The use of an efficient expression plasmid in Chaetomium globosum W7 to generate the overexpression mutant OEX13 resulted in the highest chaetoglobosin A increase to 298.77 mg/L. Interestingly, the transcription level of the polyketide synthase gene significantly fluctuated with the change in CgMfs1, confirming that the predicted efflux gene CgMfs1 could play a crucial role in chaetoglobosin A transportation. Effective efflux of chaetoglobosin A could possibly alleviate feedback inhibition, resulting in notable increase in the expression of the polyketide synthase gene. Furthermore, we utilized cornstalk as the fermentation substrate to produce chaetoglobosin A, and scanning electron microscopy and Fourier transform‐infrared spectroscopy revealed that the strain OEX13 could well degrade cornstalk, presenting significant increases in the chaetoglobosin A yield, when compared with that produced by the wild‐type strain (from 40.32 to 191.90 mg/L). Thus, this research provides a novel analogous engineering strategy for the construction of high‐yielding strain and offers new insight into large‐scale chaetoglobosin A production. John Wiley and Sons Inc. 2022-08-05 /pmc/articles/PMC9518988/ /pubmed/35930651 http://dx.doi.org/10.1111/1751-7915.14111 Text en © 2022 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Zhao, Shanshan Lin, Congyu Cheng, Ming Zhang, Kai Wang, Zhengran Zhao, Tong Yang, Qian New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum |
title | New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum
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title_full | New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum
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title_fullStr | New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum
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title_full_unstemmed | New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum
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title_short | New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum
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title_sort | new insight into the production improvement and resource generation of chaetoglobosin a in chaetomium globosum |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9518988/ https://www.ncbi.nlm.nih.gov/pubmed/35930651 http://dx.doi.org/10.1111/1751-7915.14111 |
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