From waste to health-supporting molecules: biosynthesis of natural products from lignin-, plastic- and seaweed-based monomers using metabolically engineered Streptomyces lividans
Abstract Background Transforming waste and nonfood materials into bulk biofuels and chemicals represents a major stride in creating a sustainable bioindustry to optimize the use of resources while reducing environmental footprint. However, despite these advancements, the production of high-value nat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Microbial Cell Factories |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12934-023-02266-0 |
| _version_ | 1797376738592817152 |
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| author | Kyoyoung Seo Wei Shu Christian Rückert-Reed Patrick Gerlinger Tobias J. Erb Jörn Kalinowski Christoph Wittmann |
| author_facet | Kyoyoung Seo Wei Shu Christian Rückert-Reed Patrick Gerlinger Tobias J. Erb Jörn Kalinowski Christoph Wittmann |
| author_sort | Kyoyoung Seo |
| collection | DOAJ |
| description | Abstract Background Transforming waste and nonfood materials into bulk biofuels and chemicals represents a major stride in creating a sustainable bioindustry to optimize the use of resources while reducing environmental footprint. However, despite these advancements, the production of high-value natural products often continues to depend on the use of first-generation substrates, underscoring the intricate processes and specific requirements of their biosyntheses. This is also true for Streptomyces lividans, a renowned host organism celebrated for its capacity to produce a wide array of natural products, which is attributed to its genetic versatility and potent secondary metabolic activity. Given this context, it becomes imperative to assess and optimize this microorganism for the synthesis of natural products specifically from waste and nonfood substrates. Results We metabolically engineered S. lividans to heterologously produce the ribosomally synthesized and posttranslationally modified peptide bottromycin, as well as the polyketide pamamycin. The modified strains successfully produced these compounds using waste and nonfood model substrates such as protocatechuate (derived from lignin), 4-hydroxybenzoate (sourced from plastic waste), and mannitol (from seaweed). Comprehensive transcriptomic and metabolomic analyses offered insights into how these substrates influenced the cellular metabolism of S. lividans. In terms of production efficiency, S. lividans showed remarkable tolerance, especially in a fed-batch process using a mineral medium containing the toxic aromatic 4-hydroxybenzoate, which led to enhanced and highly selective bottromycin production. Additionally, the strain generated a unique spectrum of pamamycins when cultured in mannitol-rich seaweed extract with no additional nutrients. Conclusion Our study showcases the successful production of high-value natural products based on the use of varied waste and nonfood raw materials, circumventing the reliance on costly, food-competing resources. S. lividans exhibited remarkable adaptability and resilience when grown on these diverse substrates. When cultured on aromatic compounds, it displayed a distinct array of intracellular CoA esters, presenting promising avenues for polyketide production. Future research could be focused on enhancing S. lividans substrate utilization pathways to process the intricate mixtures commonly found in waste and nonfood sources more efficiently. |
| first_indexed | 2024-03-08T19:43:03Z |
| format | Article |
| id | doaj.art-f838683782cc46d4aa8b5f0777d5904a |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-03-08T19:43:03Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-f838683782cc46d4aa8b5f0777d5904a2023-12-24T12:32:38ZengBMCMicrobial Cell Factories1475-28592023-12-0122112510.1186/s12934-023-02266-0From waste to health-supporting molecules: biosynthesis of natural products from lignin-, plastic- and seaweed-based monomers using metabolically engineered Streptomyces lividansKyoyoung Seo0Wei Shu1Christian Rückert-Reed2Patrick Gerlinger3Tobias J. Erb4Jörn Kalinowski5Christoph Wittmann6Institute of Systems Biotechnology, Saarland UniversityInstitute of Systems Biotechnology, Saarland UniversityCebitec, University of BielefeldMax Planck Institute for Terrestrial MicrobiologyMax Planck Institute for Terrestrial MicrobiologyCebitec, University of BielefeldInstitute of Systems Biotechnology, Saarland UniversityAbstract Background Transforming waste and nonfood materials into bulk biofuels and chemicals represents a major stride in creating a sustainable bioindustry to optimize the use of resources while reducing environmental footprint. However, despite these advancements, the production of high-value natural products often continues to depend on the use of first-generation substrates, underscoring the intricate processes and specific requirements of their biosyntheses. This is also true for Streptomyces lividans, a renowned host organism celebrated for its capacity to produce a wide array of natural products, which is attributed to its genetic versatility and potent secondary metabolic activity. Given this context, it becomes imperative to assess and optimize this microorganism for the synthesis of natural products specifically from waste and nonfood substrates. Results We metabolically engineered S. lividans to heterologously produce the ribosomally synthesized and posttranslationally modified peptide bottromycin, as well as the polyketide pamamycin. The modified strains successfully produced these compounds using waste and nonfood model substrates such as protocatechuate (derived from lignin), 4-hydroxybenzoate (sourced from plastic waste), and mannitol (from seaweed). Comprehensive transcriptomic and metabolomic analyses offered insights into how these substrates influenced the cellular metabolism of S. lividans. In terms of production efficiency, S. lividans showed remarkable tolerance, especially in a fed-batch process using a mineral medium containing the toxic aromatic 4-hydroxybenzoate, which led to enhanced and highly selective bottromycin production. Additionally, the strain generated a unique spectrum of pamamycins when cultured in mannitol-rich seaweed extract with no additional nutrients. Conclusion Our study showcases the successful production of high-value natural products based on the use of varied waste and nonfood raw materials, circumventing the reliance on costly, food-competing resources. S. lividans exhibited remarkable adaptability and resilience when grown on these diverse substrates. When cultured on aromatic compounds, it displayed a distinct array of intracellular CoA esters, presenting promising avenues for polyketide production. Future research could be focused on enhancing S. lividans substrate utilization pathways to process the intricate mixtures commonly found in waste and nonfood sources more efficiently.https://doi.org/10.1186/s12934-023-02266-0Streptomyces lividansRenewable feedstockLigninPolystyreneSeaweed4-hydroxybenzoate |
| spellingShingle | Kyoyoung Seo Wei Shu Christian Rückert-Reed Patrick Gerlinger Tobias J. Erb Jörn Kalinowski Christoph Wittmann From waste to health-supporting molecules: biosynthesis of natural products from lignin-, plastic- and seaweed-based monomers using metabolically engineered Streptomyces lividans Microbial Cell Factories Streptomyces lividans Renewable feedstock Lignin Polystyrene Seaweed 4-hydroxybenzoate |
| title | From waste to health-supporting molecules: biosynthesis of natural products from lignin-, plastic- and seaweed-based monomers using metabolically engineered Streptomyces lividans |
| title_full | From waste to health-supporting molecules: biosynthesis of natural products from lignin-, plastic- and seaweed-based monomers using metabolically engineered Streptomyces lividans |
| title_fullStr | From waste to health-supporting molecules: biosynthesis of natural products from lignin-, plastic- and seaweed-based monomers using metabolically engineered Streptomyces lividans |
| title_full_unstemmed | From waste to health-supporting molecules: biosynthesis of natural products from lignin-, plastic- and seaweed-based monomers using metabolically engineered Streptomyces lividans |
| title_short | From waste to health-supporting molecules: biosynthesis of natural products from lignin-, plastic- and seaweed-based monomers using metabolically engineered Streptomyces lividans |
| title_sort | from waste to health supporting molecules biosynthesis of natural products from lignin plastic and seaweed based monomers using metabolically engineered streptomyces lividans |
| topic | Streptomyces lividans Renewable feedstock Lignin Polystyrene Seaweed 4-hydroxybenzoate |
| url | https://doi.org/10.1186/s12934-023-02266-0 |
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