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Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces
Exporter engineering is a promising strategy to construct high‐yield Streptomyces for natural product pharmaceuticals in industrial biotechnology. However, available exporters are scarce, due to the limited knowledge of bacterial transporters. Here, we built a workflow for exporter mining and devise...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966021/ https://www.ncbi.nlm.nih.gov/pubmed/34437755 http://dx.doi.org/10.1111/1751-7915.13883 |
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author | Chu, Liyang Li, Shanshan Dong, Zhuoxu Zhang, Yanyan Jin, Pinjiao Ye, Lan Wang, Xiangjing Xiang, Wensheng |
author_facet | Chu, Liyang Li, Shanshan Dong, Zhuoxu Zhang, Yanyan Jin, Pinjiao Ye, Lan Wang, Xiangjing Xiang, Wensheng |
author_sort | Chu, Liyang |
collection | PubMed |
description | Exporter engineering is a promising strategy to construct high‐yield Streptomyces for natural product pharmaceuticals in industrial biotechnology. However, available exporters are scarce, due to the limited knowledge of bacterial transporters. Here, we built a workflow for exporter mining and devised a tunable plug‐and‐play exporter (TuPPE) module to improve the production of macrolide biopesticides in Streptomyces. Combining genome analyses and experimental confirmations, we found three ATP‐binding cassette transporters that contribute to milbemycin production in Streptomyces bingchenggensis. We then optimized the expression level of target exporters for milbemycin titer optimization by designing a TuPPE module with replaceable promoters and ribosome binding sites. Finally, broader applications of the TuPPE module were implemented in industrial S. bingchenggensis BC04, Streptomyces avermitilis NEAU12 and Streptomyces cyaneogriseus NMWT1, which led to optimal titer improvement of milbemycin A3/A4, avermectin B(1a) and nemadectin α by 24.2%, 53.0% and 41.0%, respectively. Our work provides useful exporters and a convenient TuPPE module for titer improvement of macrolide biopesticides in Streptomyces. More importantly, the feasible exporter mining workflow developed here might shed light on widespread applications of exporter engineering in Streptomyces to boost the production of other secondary metabolites. |
format | Online Article Text |
id | pubmed-8966021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89660212022-04-05 Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces Chu, Liyang Li, Shanshan Dong, Zhuoxu Zhang, Yanyan Jin, Pinjiao Ye, Lan Wang, Xiangjing Xiang, Wensheng Microb Biotechnol Research Articles Exporter engineering is a promising strategy to construct high‐yield Streptomyces for natural product pharmaceuticals in industrial biotechnology. However, available exporters are scarce, due to the limited knowledge of bacterial transporters. Here, we built a workflow for exporter mining and devised a tunable plug‐and‐play exporter (TuPPE) module to improve the production of macrolide biopesticides in Streptomyces. Combining genome analyses and experimental confirmations, we found three ATP‐binding cassette transporters that contribute to milbemycin production in Streptomyces bingchenggensis. We then optimized the expression level of target exporters for milbemycin titer optimization by designing a TuPPE module with replaceable promoters and ribosome binding sites. Finally, broader applications of the TuPPE module were implemented in industrial S. bingchenggensis BC04, Streptomyces avermitilis NEAU12 and Streptomyces cyaneogriseus NMWT1, which led to optimal titer improvement of milbemycin A3/A4, avermectin B(1a) and nemadectin α by 24.2%, 53.0% and 41.0%, respectively. Our work provides useful exporters and a convenient TuPPE module for titer improvement of macrolide biopesticides in Streptomyces. More importantly, the feasible exporter mining workflow developed here might shed light on widespread applications of exporter engineering in Streptomyces to boost the production of other secondary metabolites. John Wiley and Sons Inc. 2021-08-26 /pmc/articles/PMC8966021/ /pubmed/34437755 http://dx.doi.org/10.1111/1751-7915.13883 Text en © 2021 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Chu, Liyang Li, Shanshan Dong, Zhuoxu Zhang, Yanyan Jin, Pinjiao Ye, Lan Wang, Xiangjing Xiang, Wensheng Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces |
title | Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces
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title_full | Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces
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title_fullStr | Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces
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title_full_unstemmed | Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces
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title_short | Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces
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title_sort | mining and engineering exporters for titer improvement of macrolide biopesticides in streptomyces |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966021/ https://www.ncbi.nlm.nih.gov/pubmed/34437755 http://dx.doi.org/10.1111/1751-7915.13883 |
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