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Main Authors: Zheng, Gaofan, Zhou, Weiyan, Gui, Yingyue, Jiang, Yuxi, Zhu, Yunfei, Ma, Junying, Ju, Jianhua, Xin, Xiujuan, Li, Baoli, Wang, Ruida, Zhao, Ming, An, Faliang
Format: Artículo científico
Language:en
Published: Bioresource technology 2025
Subjects:
Online Access:https://pubmed.ncbi.nlm.nih.gov/40774434/
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author Zheng, Gaofan
Zhou, Weiyan
Gui, Yingyue
Jiang, Yuxi
Zhu, Yunfei
Ma, Junying
Ju, Jianhua
Xin, Xiujuan
Li, Baoli
Wang, Ruida
Zhao, Ming
An, Faliang
author_facet Zheng, Gaofan
Zhou, Weiyan
Gui, Yingyue
Jiang, Yuxi
Zhu, Yunfei
Ma, Junying
Ju, Jianhua
Xin, Xiujuan
Li, Baoli
Wang, Ruida
Zhao, Ming
An, Faliang
Zheng, Gaofan
Zhou, Weiyan
Gui, Yingyue
Jiang, Yuxi
Zhu, Yunfei
Ma, Junying
Ju, Jianhua
Xin, Xiujuan
Li, Baoli
Wang, Ruida
Zhao, Ming
An, Faliang
collection PubMed - marine biology
contents Balancing nitrogen metabolism to efficiently drive anti-tuberculosis ilamycins biosynthesis in Streptomyces atratus. Zheng, Gaofan Zhou, Weiyan Gui, Yingyue Jiang, Yuxi Zhu, Yunfei Ma, Junying Ju, Jianhua Xin, Xiujuan Li, Baoli Wang, Ruida Zhao, Ming An, Faliang Streptomyces Nitrogen Antitubercular Agents Multigene Family Fermentation Bioreactors Gene Expression Regulation, Bacterial Promoter Regions, Genetic The deep-sea-derived Streptomyces atratus SCSIO ZH16 is a promising host for producing nanomole-level anti-tuberculosis ilamycins. However, limited research on regulating the ilamycins biosynthetic gene cluster (BGC) has hindered industrial production. Our previous study found that nitrogen metabolism-related genes were upregulated in strains with enhanced ilamycins production. Since amino acids from nitrogen metabolism are key precursors, we aimed to optimize ilamycins production by balancing BGC expression and nitrogen metabolism. Using RNA-seq and hierarchical clustering, we identified the native promoter P and its modified version P, which regulate the positive regulator IlaB in ilamycins BGC. To synchronously boost ilamycins synthesis and precursor supply, we analyzed P's function via bioinformatics and validated it using an indigoidine biosynthetic model. The engineered strain ΔilaR::P-ilaB::P-phoP achieved over a dozen-fold increase in ilamycins yield. Fermentation was successfully scaled up in 5-L and 500-L bioreactors, reaching titers of 2,546.4 mg/L and 1,993.9 mg/L, respectively, significantly surpassing previously reported yields. This study highlights the industrial potential of ilamycins and provides insights into enhancing peptide compound production in Streptomyces.
format Artículo científico
id pubmed_40774434
institution PubMed
language en
publishDate 2025
publisher Bioresource technology
record_format pubmed
spellingShingle Balancing nitrogen metabolism to efficiently drive anti-tuberculosis ilamycins biosynthesis in Streptomyces atratus.
Zheng, Gaofan
Zhou, Weiyan
Gui, Yingyue
Jiang, Yuxi
Zhu, Yunfei
Ma, Junying
Ju, Jianhua
Xin, Xiujuan
Li, Baoli
Wang, Ruida
Zhao, Ming
An, Faliang
Streptomyces
Nitrogen
Antitubercular Agents
Multigene Family
Fermentation
Bioreactors
Gene Expression Regulation, Bacterial
Promoter Regions, Genetic
Balancing nitrogen metabolism to efficiently drive anti-tuberculosis ilamycins biosynthesis in Streptomyces atratus. Zheng, Gaofan Zhou, Weiyan Gui, Yingyue Jiang, Yuxi Zhu, Yunfei Ma, Junying Ju, Jianhua Xin, Xiujuan Li, Baoli Wang, Ruida Zhao, Ming An, Faliang Streptomyces Nitrogen Antitubercular Agents Multigene Family Fermentation Bioreactors Gene Expression Regulation, Bacterial Promoter Regions, Genetic The deep-sea-derived Streptomyces atratus SCSIO ZH16 is a promising host for producing nanomole-level anti-tuberculosis ilamycins. However, limited research on regulating the ilamycins biosynthetic gene cluster (BGC) has hindered industrial production. Our previous study found that nitrogen metabolism-related genes were upregulated in strains with enhanced ilamycins production. Since amino acids from nitrogen metabolism are key precursors, we aimed to optimize ilamycins production by balancing BGC expression and nitrogen metabolism. Using RNA-seq and hierarchical clustering, we identified the native promoter P and its modified version P, which regulate the positive regulator IlaB in ilamycins BGC. To synchronously boost ilamycins synthesis and precursor supply, we analyzed P's function via bioinformatics and validated it using an indigoidine biosynthetic model. The engineered strain ΔilaR::P-ilaB::P-phoP achieved over a dozen-fold increase in ilamycins yield. Fermentation was successfully scaled up in 5-L and 500-L bioreactors, reaching titers of 2,546.4 mg/L and 1,993.9 mg/L, respectively, significantly surpassing previously reported yields. This study highlights the industrial potential of ilamycins and provides insights into enhancing peptide compound production in Streptomyces.
title Balancing nitrogen metabolism to efficiently drive anti-tuberculosis ilamycins biosynthesis in Streptomyces atratus.
topic Streptomyces
Nitrogen
Antitubercular Agents
Multigene Family
Fermentation
Bioreactors
Gene Expression Regulation, Bacterial
Promoter Regions, Genetic
url https://pubmed.ncbi.nlm.nih.gov/40774434/