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Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton

Spinosyns are natural broad-spectrum biological insecticides with a double glycosylated polyketide structure that are produced by aerobic fermentation of the actinomycete, Saccharopolyspora spinosa. However, their large-scale overproduction is hindered by poorly understood bottlenecks in optimizing...

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Autores principales: An, Ziheng, Tao, Hui, Wang, Yong, Xia, Bingqing, Zou, Yang, Fu, Shuai, Fang, Fang, Sun, Xiao, Huang, Renqiong, Xia, Yao, Deng, Zixin, Liu, Ran, Liu, Tiangang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453208/
https://www.ncbi.nlm.nih.gov/pubmed/34584996
http://dx.doi.org/10.1016/j.synbio.2021.09.008
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author An, Ziheng
Tao, Hui
Wang, Yong
Xia, Bingqing
Zou, Yang
Fu, Shuai
Fang, Fang
Sun, Xiao
Huang, Renqiong
Xia, Yao
Deng, Zixin
Liu, Ran
Liu, Tiangang
author_facet An, Ziheng
Tao, Hui
Wang, Yong
Xia, Bingqing
Zou, Yang
Fu, Shuai
Fang, Fang
Sun, Xiao
Huang, Renqiong
Xia, Yao
Deng, Zixin
Liu, Ran
Liu, Tiangang
author_sort An, Ziheng
collection PubMed
description Spinosyns are natural broad-spectrum biological insecticides with a double glycosylated polyketide structure that are produced by aerobic fermentation of the actinomycete, Saccharopolyspora spinosa. However, their large-scale overproduction is hindered by poorly understood bottlenecks in optimizing the original strain, and poor adaptability of the heterologous strain to the production of spinosyn. In this study, we genetically engineered heterologous spinosyn-producer Streptomyces albus J1074 and optimized the fermentation to improve the production of spinosad (spinosyn A and spinosyn D) based on our previous work. We systematically investigated the result of overexpressing polyketide synthase genes (spnA, B, C, D, E) using a constitutive promoter on the spinosad titer in S. albus J1074. The supply of polyketide synthase precursors was then increased to further improve spinosad production. Finally, increasing or replacing the carbon source of the culture medium resulted in a final spinosad titer of ∼70 mg/L, which is the highest titer of spinosad achieved in heterologous Streptomyces species. This research provides useful strategies for efficient heterologous production of natural products.
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spelling pubmed-84532082021-09-27 Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton An, Ziheng Tao, Hui Wang, Yong Xia, Bingqing Zou, Yang Fu, Shuai Fang, Fang Sun, Xiao Huang, Renqiong Xia, Yao Deng, Zixin Liu, Ran Liu, Tiangang Synth Syst Biotechnol Article Spinosyns are natural broad-spectrum biological insecticides with a double glycosylated polyketide structure that are produced by aerobic fermentation of the actinomycete, Saccharopolyspora spinosa. However, their large-scale overproduction is hindered by poorly understood bottlenecks in optimizing the original strain, and poor adaptability of the heterologous strain to the production of spinosyn. In this study, we genetically engineered heterologous spinosyn-producer Streptomyces albus J1074 and optimized the fermentation to improve the production of spinosad (spinosyn A and spinosyn D) based on our previous work. We systematically investigated the result of overexpressing polyketide synthase genes (spnA, B, C, D, E) using a constitutive promoter on the spinosad titer in S. albus J1074. The supply of polyketide synthase precursors was then increased to further improve spinosad production. Finally, increasing or replacing the carbon source of the culture medium resulted in a final spinosad titer of ∼70 mg/L, which is the highest titer of spinosad achieved in heterologous Streptomyces species. This research provides useful strategies for efficient heterologous production of natural products. KeAi Publishing 2021-09-20 /pmc/articles/PMC8453208/ /pubmed/34584996 http://dx.doi.org/10.1016/j.synbio.2021.09.008 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
An, Ziheng
Tao, Hui
Wang, Yong
Xia, Bingqing
Zou, Yang
Fu, Shuai
Fang, Fang
Sun, Xiao
Huang, Renqiong
Xia, Yao
Deng, Zixin
Liu, Ran
Liu, Tiangang
Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton
title Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton
title_full Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton
title_fullStr Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton
title_full_unstemmed Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton
title_short Increasing the heterologous production of spinosad in Streptomyces albus J1074 by regulating biosynthesis of its polyketide skeleton
title_sort increasing the heterologous production of spinosad in streptomyces albus j1074 by regulating biosynthesis of its polyketide skeleton
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453208/
https://www.ncbi.nlm.nih.gov/pubmed/34584996
http://dx.doi.org/10.1016/j.synbio.2021.09.008
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