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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...

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Detalles Bibliográficos
Autores principales: Chu, Liyang, Li, Shanshan, Dong, Zhuoxu, Zhang, Yanyan, Jin, Pinjiao, Ye, Lan, Wang, Xiangjing, Xiang, Wensheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
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.
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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
title_full Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces
title_fullStr Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces
title_full_unstemmed Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces
title_short Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces
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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