Tuning of fed-batch cultivation of Streptomyces clavuligerus for enhanced Clavulanic Acid production based on genome-scale dynamic modeling

Rios, David; Ramírez-Malule, Howard; Neubauer, Peter; Junne, Stefan; Ríos‐Estepa, Rigoberto; Ochoa, Silvia

doi:10.1016/j.bej.2022.108534

Cited by 2 publications

(2 citation statements)

References 28 publications

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“…Previous studies indicated that the central carbon metabolism (including glycolysis, TCA cycles, and pentose phosphate pathway) was the main carbon metabolic pathway of the Streptomyces genus. , In a cocultured strains (Chlorella vulgaris and Saccharomycopsis fibuligera) consortium, the expressions of most genes encoding the conversion from glucose to pyruvate of Chlorella vulgaris (glycolysis pathway) were significantly up-regulated, indicating a highly stimulated consumption of glucose by the Chlorella vulgaris . The stronger carbon source metabolism performance (especially carbohydrate) of the strains coculture in this study indicated that the glycolysis pathway was significantly enhanced.…”

Section: Resultsmentioning

confidence: 47%

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Aerobic Denitrification Promoting by Actinomycetes Coculture: Investigating Performance, Carbon Source Metabolic Characteristic, and Raw Water Restoration

Ma,

Yang,

et al. 2023

Environ. Sci. Technol.

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The coculture theory that promotes denitrification relies on effectively utilizing the resources of low-efficiency denitrification microbes. Here, the strains Streptomyces sp. PYX97 and Streptomyces sp. TSJ96 were isolated and showed lower denitrification capacity when cultured individually. However, the coculture of strains PYX97 and TSJ96 enhanced nitrogen removal (removed 96.40% of total nitrogen) and organic carbon reduction (removed 92.13% of dissolved organic carbon) under aerobic conditions. Nitrogen balance analysis indicated that coculturing enhanced the efficiency of nitrate converted into gaseous nitrogen reaching 70.42%. Meanwhile, the coculturing promoted the cell metabolism capacity and carbon source metabolic activity. The coculture strains PYX97 and TSJ96 thrived in conditions of C/N = 10, alkalescence, and 150 rpm shaking speed. The coculturing reduced total nitrogen and COD Mn in the raw water treatment by 83.32 and 84.21%, respectively. During this treatment, the cell metabolic activity and cell density increased in the coculture strains PYX97 and TSJ96 reactor. Moreover, the coculture strains could utilize aromatic protein and soluble microbial products during aerobic denitrification processes in raw water treatment. This study suggests that coculturing inefficient actinomycete strains could be a promising approach for treating polluted water bodies.

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Section: Resultsmentioning

confidence: 47%

“…Moreover, the potential quorum sensing and syntrophic pathway between the two strains drove specific pollutant removal. Therefore, the cross-feeding, quorum sensing, and syntrophic pathway might be the cooperation mechanism for two strains of actinomycetes coculture. ,− …”

Section: Resultsmentioning

confidence: 99%

Aerobic Denitrification Promoting by Actinomycetes Coculture: Investigating Performance, Carbon Source Metabolic Characteristic, and Raw Water Restoration

Ma,

Yang,

et al. 2023

Environ. Sci. Technol.

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Clavulanic Acid Overproduction: A Review of Environmental Conditions, Metabolic Fluxes, and Strain Engineering in Streptomyces clavuligerus

Gómez-Ríos,

Gómez-Gaona,

Ramírez-Malule

2024

Fermentation

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Clavulanic acid is a potent β-lactamase inhibitor produced by Streptomyces clavuligerus, widely used in combination with β-lactam antibiotics to combat antimicrobial resistance. This systematic review analyzes the most successful methodologies for clavulanic acid overproduction, focusing on the highest yields reported in bench-scale and bioreactor-scale fermentations. Studies have demonstrated that glycerol is the preferred carbon source for clavulanic acid production over other sources like starch and dextrins. The optimization of feeding strategies, especially in fed-batch operations, has improved glycerol utilization and extended the clavulanic acid production phase. Organic nitrogen sources, particularly soybean protein isolates and amino acid supplements such as L-arginine, L-threonine, and L-glutamate, have been proven effective at increasing CA yields both in batch and fed-batch cultures, especially when balanced with appropriate carbon sources. Strain engineering approaches, including mutagenesis and targeted genetic modifications, have allowed for the obtainment of overproducer S. clavuligerus strains. Specifically, engineering efforts that overexpress key regulatory genes such as ccaR and claR, or that disrupt competing pathways, redirect the metabolic flux towards CA biosynthesis, leading to high clavulanic acid titers. The fed-batch operation at the bioreactor scale emerges as the most feasible alternative for prolonged clavulanic acid production with both wild-type and mutant strains, allowing for the attainment of high titers during cultivations.

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Tuning of fed-batch cultivation of Streptomyces clavuligerus for enhanced Clavulanic Acid production based on genome-scale dynamic modeling

Cited by 2 publications

References 28 publications

Aerobic Denitrification Promoting by Actinomycetes Coculture: Investigating Performance, Carbon Source Metabolic Characteristic, and Raw Water Restoration

Aerobic Denitrification Promoting by Actinomycetes Coculture: Investigating Performance, Carbon Source Metabolic Characteristic, and Raw Water Restoration

Clavulanic Acid Overproduction: A Review of Environmental Conditions, Metabolic Fluxes, and Strain Engineering in Streptomyces clavuligerus

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