Enhancing armeniaspirols production through multi-level engineering of a native Streptomyces producer
Abstract Background Nature has provided unique molecular scaffolds for applications including therapeutics, agriculture, and food. Due to differences in ecological environments and laboratory conditions, engineering is often necessary to uncover and utilize the chemical diversity. Although we can ef...
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Microbial Cell Factories |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12934-023-02092-4 |
| _version_ | 1797836137009512448 |
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| author | Elena Heng Yi Wee Lim Chung Yan Leong Veronica W. P. Ng Siew Bee Ng Yee Hwee Lim Fong Tian Wong |
| author_facet | Elena Heng Yi Wee Lim Chung Yan Leong Veronica W. P. Ng Siew Bee Ng Yee Hwee Lim Fong Tian Wong |
| author_sort | Elena Heng |
| collection | DOAJ |
| description | Abstract Background Nature has provided unique molecular scaffolds for applications including therapeutics, agriculture, and food. Due to differences in ecological environments and laboratory conditions, engineering is often necessary to uncover and utilize the chemical diversity. Although we can efficiently activate and mine these often complex 3D molecules, sufficient production of target molecules for further engineering and application remain a considerable bottleneck. An example of these bioactive scaffolds is armeniaspirols, which are potent polyketide antibiotics against gram-positive pathogens and multi-resistance gram-negative Helicobacter pylori. Here, we examine the upregulation of armeniaspirols in an alternative Streptomyces producer, Streptomyces sp. A793. Results Through an incidental observation of enhanced yields with the removal of a competing polyketide cluster, we observed seven-fold improvement in armeniaspirol production. To further investigate the improvement of armeniaspirol production, we examine upregulation of armeniaspirols through engineering of biosynthetic pathways and primary metabolism; including perturbation of genes in biosynthetic gene clusters and regulation of triacylglycerols pool. Conclusion With either overexpression of extender unit pathway or late-stage N-methylation, or the deletion of a competing polyketide cluster, we can achieve seven-fold to forty nine-fold upregulation of armeniaspirol production. The most significant upregulation was achieved by expression of heterologous fatty acyl-CoA synthase, where we observed not only a ninety seven-fold increase in production yields compared to wild type, but also an increase in the diversity of observed armeniaspirol intermediates and analogs. |
| first_indexed | 2024-04-09T15:04:55Z |
| format | Article |
| id | doaj.art-33aca800c1b043e2a456110633620690 |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-04-09T15:04:55Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-33aca800c1b043e2a4561106336206902023-04-30T11:32:20ZengBMCMicrobial Cell Factories1475-28592023-04-012211810.1186/s12934-023-02092-4Enhancing armeniaspirols production through multi-level engineering of a native Streptomyces producerElena Heng0Yi Wee Lim1Chung Yan Leong2Veronica W. P. Ng3Siew Bee Ng4Yee Hwee Lim5Fong Tian Wong6Molecular Engineering Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Chemical Biotechnology and Biocatalysis, Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR)Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR)Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR)Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR)Chemical Biotechnology and Biocatalysis, Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR)Molecular Engineering Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Abstract Background Nature has provided unique molecular scaffolds for applications including therapeutics, agriculture, and food. Due to differences in ecological environments and laboratory conditions, engineering is often necessary to uncover and utilize the chemical diversity. Although we can efficiently activate and mine these often complex 3D molecules, sufficient production of target molecules for further engineering and application remain a considerable bottleneck. An example of these bioactive scaffolds is armeniaspirols, which are potent polyketide antibiotics against gram-positive pathogens and multi-resistance gram-negative Helicobacter pylori. Here, we examine the upregulation of armeniaspirols in an alternative Streptomyces producer, Streptomyces sp. A793. Results Through an incidental observation of enhanced yields with the removal of a competing polyketide cluster, we observed seven-fold improvement in armeniaspirol production. To further investigate the improvement of armeniaspirol production, we examine upregulation of armeniaspirols through engineering of biosynthetic pathways and primary metabolism; including perturbation of genes in biosynthetic gene clusters and regulation of triacylglycerols pool. Conclusion With either overexpression of extender unit pathway or late-stage N-methylation, or the deletion of a competing polyketide cluster, we can achieve seven-fold to forty nine-fold upregulation of armeniaspirol production. The most significant upregulation was achieved by expression of heterologous fatty acyl-CoA synthase, where we observed not only a ninety seven-fold increase in production yields compared to wild type, but also an increase in the diversity of observed armeniaspirol intermediates and analogs.https://doi.org/10.1186/s12934-023-02092-4Natural productsBiosynthetic engineeringUpregulationArmeniaspirolsStreptomycesFatty acyl-CoA synthase |
| spellingShingle | Elena Heng Yi Wee Lim Chung Yan Leong Veronica W. P. Ng Siew Bee Ng Yee Hwee Lim Fong Tian Wong Enhancing armeniaspirols production through multi-level engineering of a native Streptomyces producer Microbial Cell Factories Natural products Biosynthetic engineering Upregulation Armeniaspirols Streptomyces Fatty acyl-CoA synthase |
| title | Enhancing armeniaspirols production through multi-level engineering of a native Streptomyces producer |
| title_full | Enhancing armeniaspirols production through multi-level engineering of a native Streptomyces producer |
| title_fullStr | Enhancing armeniaspirols production through multi-level engineering of a native Streptomyces producer |
| title_full_unstemmed | Enhancing armeniaspirols production through multi-level engineering of a native Streptomyces producer |
| title_short | Enhancing armeniaspirols production through multi-level engineering of a native Streptomyces producer |
| title_sort | enhancing armeniaspirols production through multi level engineering of a native streptomyces producer |
| topic | Natural products Biosynthetic engineering Upregulation Armeniaspirols Streptomyces Fatty acyl-CoA synthase |
| url | https://doi.org/10.1186/s12934-023-02092-4 |
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