Constitutive hyperproduction of sorbicillinoids in Trichoderma reesei ZC121
Abstract Background In addition to its outstanding cellulase production ability, Trichoderma reesei produces a wide variety of valuable secondary metabolites, the production of which has not received much attention to date. Among them, sorbicillinoids, a large group of hexaketide secondary metabolit...
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| Language: | English |
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BMC
2018-10-01
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| Series: | Biotechnology for Biofuels |
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| Online Access: | http://link.springer.com/article/10.1186/s13068-018-1296-4 |
| _version_ | 1818263226717044736 |
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| author | Chengcheng Li Fengming Lin Wei Sun Shaoxun Yuan Zhihua Zhou Fu-Gen Wu Zhan Chen |
| author_facet | Chengcheng Li Fengming Lin Wei Sun Shaoxun Yuan Zhihua Zhou Fu-Gen Wu Zhan Chen |
| author_sort | Chengcheng Li |
| collection | DOAJ |
| description | Abstract Background In addition to its outstanding cellulase production ability, Trichoderma reesei produces a wide variety of valuable secondary metabolites, the production of which has not received much attention to date. Among them, sorbicillinoids, a large group of hexaketide secondary metabolites derived from polyketides, are drawing a growing interest from researchers because they exhibit a variety of important biological functions, including anticancer, antioxidant, antiviral, and antimicrobial properties. The development of fungi strains with constitutive, hyperproduction of sorbicillinoids is thus desired for future industry application but is not well-studied. Moreover, although T. reesei has been demonstrated to produce sorbicillinoids with the corresponding gene cluster and biosynthesis pathway proposed, the underlying molecular mechanism governing sorbicillinoid biosynthesis remains unknown. Results Recombinant T. reesei ZC121 was constructed from strain RUT-C30 by the insertion of the gene 12121-knockout cassette at the telomere of T. reesei chromosome IV in consideration of the off-target mutagenesis encountered during the unsuccessful deletion of gene 121121. Strain ZC121, when grown on cellulose, showed a sharp reduction of cellulase production, but yet a remarkable enhancement of sorbicillinoids production as compared to strain RUT-C30. The hyperproduction of sorbicillinoids is a constitutive process, independent of culture conditions such as carbon source, light, pH, and temperature. To the best of our knowledge, strain ZC121 displays record sorbicillinoid production levels when grown on both glucose and cellulose. Sorbicillinol and bisvertinolone are the two major sorbicillinoid compounds produced. ZC121 displayed a different morphology and markedly reduced sporulation compared to RUT-C30 but had a similar growth rate and biomass. Transcriptome analysis showed that most genes involved in cellulase production were downregulated significantly in ZC121 grown on cellulose, whereas remarkably all genes in the sorbicillinoid gene cluster were upregulated on both cellulose and glucose. Conclusion A constitutive sorbicillinoid-hyperproduction strain T. reesei ZC121 was obtained by off-target mutagenesis, displaying an overwhelming shift from cellulase production to sorbicillinoid production on cellulose, leading to a record for sorbicillinoid production. For the first time, T. reesei degraded cellulose to produce platform chemical compounds other than protein in high yield. We propose that the off-target mutagenesis occurring at the telomere region might cause chromosome remodeling and subsequently alter the cell structure and the global gene expression pattern of strain ZC121, as shown by phenotype profiling and comparative transcriptome analysis of ZC121. Overall, T. reesei ZC121 holds great promise for the industrial production of sorbicillinoids and serves as a good model to explore the regulation mechanism of sorbicillinoids’ biosynthesis. |
| first_indexed | 2024-12-12T19:15:39Z |
| format | Article |
| id | doaj.art-62776d446ff74655888e724e2f6110df |
| institution | Directory Open Access Journal |
| issn | 1754-6834 |
| language | English |
| last_indexed | 2024-12-12T19:15:39Z |
| publishDate | 2018-10-01 |
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| spelling | doaj.art-62776d446ff74655888e724e2f6110df2022-12-22T00:14:44ZengBMCBiotechnology for Biofuels1754-68342018-10-0111111610.1186/s13068-018-1296-4Constitutive hyperproduction of sorbicillinoids in Trichoderma reesei ZC121Chengcheng Li0Fengming Lin1Wei Sun2Shaoxun Yuan3Zhihua Zhou4Fu-Gen Wu5Zhan Chen6State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast UniversityState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast UniversityState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast UniversityState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast UniversityKey Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast UniversityDepartment of Chemistry, University of MichiganAbstract Background In addition to its outstanding cellulase production ability, Trichoderma reesei produces a wide variety of valuable secondary metabolites, the production of which has not received much attention to date. Among them, sorbicillinoids, a large group of hexaketide secondary metabolites derived from polyketides, are drawing a growing interest from researchers because they exhibit a variety of important biological functions, including anticancer, antioxidant, antiviral, and antimicrobial properties. The development of fungi strains with constitutive, hyperproduction of sorbicillinoids is thus desired for future industry application but is not well-studied. Moreover, although T. reesei has been demonstrated to produce sorbicillinoids with the corresponding gene cluster and biosynthesis pathway proposed, the underlying molecular mechanism governing sorbicillinoid biosynthesis remains unknown. Results Recombinant T. reesei ZC121 was constructed from strain RUT-C30 by the insertion of the gene 12121-knockout cassette at the telomere of T. reesei chromosome IV in consideration of the off-target mutagenesis encountered during the unsuccessful deletion of gene 121121. Strain ZC121, when grown on cellulose, showed a sharp reduction of cellulase production, but yet a remarkable enhancement of sorbicillinoids production as compared to strain RUT-C30. The hyperproduction of sorbicillinoids is a constitutive process, independent of culture conditions such as carbon source, light, pH, and temperature. To the best of our knowledge, strain ZC121 displays record sorbicillinoid production levels when grown on both glucose and cellulose. Sorbicillinol and bisvertinolone are the two major sorbicillinoid compounds produced. ZC121 displayed a different morphology and markedly reduced sporulation compared to RUT-C30 but had a similar growth rate and biomass. Transcriptome analysis showed that most genes involved in cellulase production were downregulated significantly in ZC121 grown on cellulose, whereas remarkably all genes in the sorbicillinoid gene cluster were upregulated on both cellulose and glucose. Conclusion A constitutive sorbicillinoid-hyperproduction strain T. reesei ZC121 was obtained by off-target mutagenesis, displaying an overwhelming shift from cellulase production to sorbicillinoid production on cellulose, leading to a record for sorbicillinoid production. For the first time, T. reesei degraded cellulose to produce platform chemical compounds other than protein in high yield. We propose that the off-target mutagenesis occurring at the telomere region might cause chromosome remodeling and subsequently alter the cell structure and the global gene expression pattern of strain ZC121, as shown by phenotype profiling and comparative transcriptome analysis of ZC121. Overall, T. reesei ZC121 holds great promise for the industrial production of sorbicillinoids and serves as a good model to explore the regulation mechanism of sorbicillinoids’ biosynthesis.http://link.springer.com/article/10.1186/s13068-018-1296-4Biosynthetic gene clusterSecondary metabolitesNatural productYellow pigmentSorbicillinoidsTrichoderma reesei |
| spellingShingle | Chengcheng Li Fengming Lin Wei Sun Shaoxun Yuan Zhihua Zhou Fu-Gen Wu Zhan Chen Constitutive hyperproduction of sorbicillinoids in Trichoderma reesei ZC121 Biotechnology for Biofuels Biosynthetic gene cluster Secondary metabolites Natural product Yellow pigment Sorbicillinoids Trichoderma reesei |
| title | Constitutive hyperproduction of sorbicillinoids in Trichoderma reesei ZC121 |
| title_full | Constitutive hyperproduction of sorbicillinoids in Trichoderma reesei ZC121 |
| title_fullStr | Constitutive hyperproduction of sorbicillinoids in Trichoderma reesei ZC121 |
| title_full_unstemmed | Constitutive hyperproduction of sorbicillinoids in Trichoderma reesei ZC121 |
| title_short | Constitutive hyperproduction of sorbicillinoids in Trichoderma reesei ZC121 |
| title_sort | constitutive hyperproduction of sorbicillinoids in trichoderma reesei zc121 |
| topic | Biosynthetic gene cluster Secondary metabolites Natural product Yellow pigment Sorbicillinoids Trichoderma reesei |
| url | http://link.springer.com/article/10.1186/s13068-018-1296-4 |
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