Enhanced Biosynthesis of Phenazine-1,6-dicarboxylic Acid in <i>Streptomyces coelicolor</i>

Deng, Ruxiang; Li, Huiling; Meng, Fei; Jia, Dan; Wang, Wei; Hu, Hongbo; Zhang, Xuehong

doi:10.1021/acssuschemeng.3c04768

ACS Sustainable Chem. Eng.

2023

DOI: 10.1021/acssuschemeng.3c04768

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Enhanced Biosynthesis of Phenazine-1,6-dicarboxylic Acid in Streptomyces coelicolor

Ruxiang Deng,

Huiling Li,

Fei Meng

et al.

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Cited by 3 publications

References 70 publications

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Chemical constituents from the pericarps of Zanthoxylum bungeanum Maxim. and their chemotaxonomic significance

Ma,

Mohamed,

et al. 2025

Biochemical Systematics and Ecology

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Chemical constituents from the pericarps of Zanthoxylum bungeanum Maxim. and their chemotaxonomic significance

Ma,

Mohamed,

et al. 2025

Biochemical Systematics and Ecology

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Enhancing the Production of ε-Poly-l-Lysine by Engineering the Sucrose Metabolism Pathway in Streptomyces albulus PD-1 Using Cane Molasses

Liu,

Chen,

et al. 2024

J. Agric. Food Chem.

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Cane molasses, a sugar-rich agro-industrial byproduct, was used to enhance the production of ε-poly-L-lysine (ε-PL) in Streptomyces albulus PD-1 as a cost-effective carbon source. The sucrose metabolism pathway was engineered by heterologously expressing sucrose-6-phosphate hydrolase from Escherichia coli W. The optimization of various promoters identified the SP44 promoter, increasing the total sugar utilization rate by 2.76-fold compared with the ermEp* promoter. Additionally, adaptive laboratory evolution improved the total sugar utilization rate. The evolved strain achieved an ε-PL titer of 2.65 ± 0.15 g/L in flask experiments, increasing the ε-PL titer by 7.16-fold compared with the unevolved strain. Comparative transcriptomic analyses revealed that the enhanced tolerance of the evolved strain to high concentrations of cane molasses was primarily due to modifications in the sucrose metabolism pathways, microbial metabolism in heavy metals and phenols, and the amino acids transport and metabolic pathways. These changes enabled more efficient ε-PL production. During fed-batch fermentation in a 5-L fermentor using a concentration of 50 g/L cane molasses, the ε-PL titer reached 36.88 ± 0.62 g/L, and dry cell weight was 41.1 ± 1.0 g/L. This study illustrates that cane molasses is an economical carbon source for producing ε-PL on an industrial scale.

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Characterization of Lomofungin Gene Cluster Enables the Biosynthesis of Related Phenazine Derivatives

Deng,

Li,

Sheng

et al. 2024

ACS Synth. Biol.

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Phenazine-based small molecules are nitrogen-containing heterocyclic compounds with diverse bioactivities and electron transfer properties that exhibit promising applications in pharmaceutical and electrochemical industries. However, the biosynthetic mechanism of highly substituted natural phenazines remains poorly understood. In this study, we report the direct cloning and heterologous expression of the lomofungin biosynthetic gene cluster (BGC) from Streptomyces lomondensis S015. Reconstruction and overexpression of the BGCs in Streptomyces coelicolor M1152 resulted in eight phenazine derivatives including two novel hybrid phenazine metabolites, and the biosynthetic pathway of lomofungin was proposed. Furthermore, gene deletion suggested that NAD(P)H-dependent oxidoreductase gene lomo14 is a nonessential gene in the biosynthesis of lomofungin. Cytotoxicity evaluation of the isolated phenazines and lomofungin was performed. Specifically, lomofungin shows substantial inhibition against two human cancer cells, HCT116 and 5637. These results provide insights into the biosynthetic mechanism of lomofungin, which will be useful for the directed biosynthesis of natural phenazine derivatives.

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Enhanced Biosynthesis of Phenazine-1,6-dicarboxylic Acid in Streptomyces coelicolor

Cited by 3 publications

References 70 publications

Chemical constituents from the pericarps of Zanthoxylum bungeanum Maxim. and their chemotaxonomic significance

Chemical constituents from the pericarps of Zanthoxylum bungeanum Maxim. and their chemotaxonomic significance

Enhancing the Production of ε-Poly-l-Lysine by Engineering the Sucrose Metabolism Pathway in Streptomyces albulus PD-1 Using Cane Molasses

Characterization of Lomofungin Gene Cluster Enables the Biosynthesis of Related Phenazine Derivatives

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