New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum
Abstract 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....
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-10-01
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| Series: | Microbial Biotechnology |
| Online Access: | https://doi.org/10.1111/1751-7915.14111 |
| _version_ | 1828110199258349568 |
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| author | Shanshan Zhao Congyu Lin Ming Cheng Kai Zhang Zhengran Wang Tong Zhao Qian Yang |
| author_facet | Shanshan Zhao Congyu Lin Ming Cheng Kai Zhang Zhengran Wang Tong Zhao Qian Yang |
| author_sort | Shanshan Zhao |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T11:16:03Z |
| format | Article |
| id | doaj.art-4e4874dab0734f5dbabc3bf8e0a417f2 |
| institution | Directory Open Access Journal |
| issn | 1751-7915 |
| language | English |
| last_indexed | 2024-04-11T11:16:03Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Microbial Biotechnology |
| spelling | doaj.art-4e4874dab0734f5dbabc3bf8e0a417f22022-12-22T04:27:14ZengWileyMicrobial Biotechnology1751-79152022-10-0115102562257710.1111/1751-7915.14111New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosumShanshan Zhao0Congyu Lin1Ming Cheng2Kai Zhang3Zhengran Wang4Tong Zhao5Qian Yang6School of Life Science and Technology Harbin Institute of Technology Harbin ChinaSchool of Life Science and Technology Harbin Institute of Technology Harbin ChinaSchool of Life Science and Technology Harbin Institute of Technology Harbin ChinaSchool of Life Science and Technology Harbin Institute of Technology Harbin ChinaSchool of Life Science and Technology Harbin Institute of Technology Harbin ChinaSchool of Life Science and Technology Harbin Institute of Technology Harbin ChinaSchool of Life Science and Technology Harbin Institute of Technology Harbin ChinaAbstract 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.https://doi.org/10.1111/1751-7915.14111 |
| spellingShingle | Shanshan Zhao Congyu Lin Ming Cheng Kai Zhang Zhengran Wang Tong Zhao Qian Yang New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum Microbial Biotechnology |
| title | New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum |
| title_full | New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum |
| title_fullStr | New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum |
| title_full_unstemmed | New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum |
| title_short | New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum |
| title_sort | new insight into the production improvement and resource generation of chaetoglobosin a in chaetomium globosum |
| url | https://doi.org/10.1111/1751-7915.14111 |
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