Genome-based rational engineering of Actinoplanes deccanensis for improving fidaxomicin production and genetic stability

Liu, Yueping; Bu, Qing-Ting; Li, Jifeng; Xie, Huang; Su, Yi-Ting; Du, Yi‐Ling; Li, Yongquan

doi:10.1016/j.biortech.2021.124982

Cited by 15 publications

(12 citation statements)

References 39 publications

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“…In our hands, D. aurantiacum was found to be very difficult to cultivate. Instead, we turned to the genetically tractable actinobacterium A. deccanensis [26–28] . Previous studies and patents describe cultivation of A. deccanensis and genetically engineered A. deccanensis strains, resulting in Fdx titers of 65.6 mg/L (not isolated), [29] 130 mg/L (not isolated), [30] 619 mg/L (not isolated), [28] 900 mg/L (not isolated), [31] and >1500 mg/L (crude) [32] .…”

Section: Resultsmentioning

confidence: 99%

“…Instead, we turned to the genetically tractable actinobacterium A. deccanensis [26–28] . Previous studies and patents describe cultivation of A. deccanensis and genetically engineered A. deccanensis strains, resulting in Fdx titers of 65.6 mg/L (not isolated), [29] 130 mg/L (not isolated), [30] 619 mg/L (not isolated), [28] 900 mg/L (not isolated), [31] and >1500 mg/L (crude) [32] . We optimized media composition and growth parameters and found that temperature, flask shape and size, and time were the most influential parameters.…”

Section: Resultsmentioning

confidence: 99%

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Isolation of Fidaxomicin and Shunt Metabolites from Actinoplanes deccanensis

Jung,

Hunter,

Dorst

et al. 2024

Helvetica Chimica Acta

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A protocol for the isolation of the antibiotic fidaxomicin (Fdx) from Actinoplanes deccanensis and the isolation of shunt metabolites from A. deccanensisfdxG2‐ is reported. We constructed the mutant strain A. deccanensisfdxG2‐ by genetic manipulation which enabled the isolation of shunt metabolites as useful starting points for semisynthetic analogues of Fdx. Furthermore, a synthetic protocol for the conversion of complex A. deccanensisfdxG2‐ extracts into the single compound FdxG2‐OH via methanolysis is presented. This synthetic procedure is complemented by images and practical notes. Full structure assignment is given in the SI and the characterization data files are published to aid experimentalists. The protocol is also suitable as an undergraduate laboratory project. We hope to facilitate research into new Fdx derivatives through the availability of this procedure.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Isolation of Fidaxomicin and Shunt Metabolites from Actinoplanes deccanensis

Jung,

Hunter,

Dorst

et al. 2024

Helvetica Chimica Acta

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“…Increasing the copy number of BGC is an effective way to increase the yield of natural products ( Li et al, 2021c ). A previous study showed that daptomycin BGC with only 65 kb length was enough to be heterologously expressed in daptomycin non-producing strain S. coelicolor M511 and successfully led to the production of 28.9 mg/l daptomycin ( Choi et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…Notably, pigments are sometimes found as byproducts of the antibiotic biosynthesis process. Reseachers improved the fidaxomicin production by removing the orange pigment byproduct in an industrial strain Actinoplanes deccanensis YP-1 ( Li et al, 2021c ).…”

Section: Introductionmentioning

confidence: 99%

Improving the Yield and Quality of Daptomycin in Streptomyces roseosporus by Multilevel Metabolic Engineering

Lyu

Fang

et al. 2022

Front. Microbiol.

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Daptomycin is a cyclic lipopeptide antibiotic with a significant antibacterial action against antibiotic-resistant Gram-positive bacteria. Despite numerous attempts to enhance daptomycin yield throughout the years, the production remains unsatisfactory. This study reports the application of multilevel metabolic engineering strategies in Streptomyces roseosporus to reconstruct high-quality daptomycin overproducing strain L2797-VHb, including precursor engineering (i.e., refactoring kynurenine pathway), regulatory pathway reconstruction (i.e., knocking out negative regulatory genes arpA and phaR), byproduct engineering (i.e., removing pigment), multicopy biosynthetic gene cluster (BGC), and fermentation process engineering (i.e., enhancing O2 supply). The daptomycin titer of L2797-VHb arrived at 113 mg/l with 565% higher comparing the starting strain L2790 (17 mg/l) in shake flasks and was further increased to 786 mg/l in 15 L fermenter. This multilevel metabolic engineering method not only effectively increases daptomycin production, but can also be applied to enhance antibiotic production in other industrial strains.

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“…Makitrynskyy developed a manipulation of AdpA regions of Streptomyces ghangensis ( S. ghangensis ) ( Makitrynskyy et al, 2021 ) , giving researchers the understanding of a metabolic pathway to improve a specific antimicrobial biosynthesis. By understanding metabolic pathways and applying different gene engineering techniques, research can improve antimicrobial production through punctual modifications to regulate specific genes, demonstrating that genetic modifications to control biosynthesis pathways could improve antimicrobial production and its activities ( Song et al, 2017 ; Li D. et al, 2021 ; Li Y.-P. et al, 2021 ).…”

Section: Genetic Engineering To Enhance Antibiotic Productionmentioning

confidence: 99%

Synthetic Biology Tools for Engineering Microbial Cells to Fight Superbugs

León-Buitimea

Balderas-Cisneros

Garza-Cárdenas

et al. 2022

Front. Bioeng. Biotechnol.

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With the increase in clinical cases of bacterial infections with multiple antibiotic resistance, the world has entered a health crisis. Overuse, inappropriate prescribing, and lack of innovation of antibiotics have contributed to the surge of microorganisms that can overcome traditional antimicrobial treatments. In 2017, the World Health Organization published a list of pathogenic bacteria, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli (ESKAPE). These bacteria can adapt to multiple antibiotics and transfer their resistance to other organisms; therefore, studies to find new therapeutic strategies are needed. One of these strategies is synthetic biology geared toward developing new antimicrobial therapies. Synthetic biology is founded on a solid and well-established theoretical framework that provides tools for conceptualizing, designing, and constructing synthetic biological systems. Recent developments in synthetic biology provide tools for engineering synthetic control systems in microbial cells. Applying protein engineering, DNA synthesis, and in silico design allows building metabolic pathways and biological circuits to control cellular behavior. Thus, synthetic biology advances have permitted the construction of communication systems between microorganisms where exogenous molecules can control specific population behaviors, induce intracellular signaling, and establish co-dependent networks of microorganisms.

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Genome-based rational engineering of Actinoplanes deccanensis for improving fidaxomicin production and genetic stability

Cited by 15 publications

References 39 publications

Isolation of Fidaxomicin and Shunt Metabolites from Actinoplanes deccanensis

Isolation of Fidaxomicin and Shunt Metabolites from Actinoplanes deccanensis

Improving the Yield and Quality of Daptomycin in Streptomyces roseosporus by Multilevel Metabolic Engineering

Synthetic Biology Tools for Engineering Microbial Cells to Fight Superbugs

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