Biosynthetic pathway of peucemycin and identification of its derivative from Streptomyces peucetius

Magar, Rubin Thapa; Pham, Van Thuy Thi; Poudel, Purna Bahadur; Nguyen, Hue Thi; Bridget, Adzemye Fovennso; Sohng, Jae Kyung

doi:10.1007/s00253-023-12385-8

Cited by 3 publications

(7 citation statements)

References 72 publications

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“…These findings led to the conclusion that the newly discovered compound was hydroxylated peucemycin. Furthermore, the compound had absorbance maxima of 200.7346, 215.7346, and 265.7347 nm similar to peucemycin and peucemycin A (Magar et al 2023 ; Pham et al 2021 ) (Fig. 1 ).…”

Section: Resultsmentioning

confidence: 69%

“…In this work, a new peucemycin derivative (peucemycin B) was isolated, and both the pathway-specific regulator (PeuR) and global regulator (BldA) were investigated as targets for the improvement of the production of peucemycin and its derivatives. The newly identified derivative is synthesized from the hydroxylation at C-19 of peucemycin suggesting a separate hydroxylation step distinct from the C-25 hydroxylation of peucemycin A biosynthesis (Magar et al 2023 ). The Peu BGC analysis provides insight into the likelihood that the PeuK is involved in the biosynthesis of peucemycin B (Magar et al 2023 ).…”

Section: Discussionmentioning

confidence: 99%

“…The compound exhibited antibacterial activities against some pathogens and suppressed the viability of various cancer cell lines (Pham et al 2021 ). Recently, a new peucemycin derivative and its putative biosynthetic gene cluster were identified, providing insight into the biosynthesis of peucemycin and its derivatives (Magar et al 2023 ). The newly identified derivative was 25-hydroxy peucemycin (peucemycin A) and had antibacterial activities against some pathogens (Magar et al 2023 ).…”

Section: Introductionmentioning

confidence: 99%

“…The peucemycin biosynthetic gene cluster (Peu BGC) has two cluster-situated regulators (pathway-specific regulators). Among the two, PeuR was identified as a Streptomyces antibiotic regulator protein (SARP) regulator having a helix-turn-helix (HTH) DNA-binding domain motif at the N-terminal and a bacterial transcriptional activator domain (BTAD) at their C terminus (Hindra and Elliot 2010 ; Magar et al 2023 ). It is currently unknown how PeuR controls the production of peucemycin and its derivatives.…”

Section: Introductionmentioning

confidence: 99%

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A new peucemycin derivative and impacts of peuR and bldA on peucemycin biosynthesis in Streptomyces peucetius

Magar,

Pham,

Poudel

et al. 2024

Appl Microbiol Biotechnol

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Streptomyces peucetius ATCC 27952 is known to produce a variety of secondary metabolites, including two important antitumor anthracyclines: daunorubicin and doxorubicin. Identification of peucemycin and 25-hydroxy peucemycin (peucemycin A), as well as their biosynthetic pathway, has expanded its biosynthetic potential. In this study, we isolated a new peucemycin derivative and identified it as 19-hydroxy peucemycin (peucemycin B). Its antibacterial activity was lower than those of peucemycin and peucemycin A. On the other hand, this newly identified peucemycin derivative had higher anticancer activity than the other two compounds for MKN45, NCI-H1650, and MDA-MB-231 cancer cell lines with IC50 values of 76.97 µM, 99.68 µM, and 135.2 µM, respectively. Peucemycin biosynthetic gene cluster revealed the presence of a SARP regulator named PeuR whose role was unknown. The presence of the TTA codon in the peuR and the absence of global regulator BldA in S. peucetius reduced its ability to regulate the peucemycin biosynthetic gene cluster. Hence, different mutants harboring these genes were prepared. S. peucetius bldA25 harboring bldA produced 1.75 times and 1.77 times more peucemycin A (11.8 mg/L) and peucemycin B (21.2 mg/L), respectively, than the wild type. On the other hand, S. peucetius R25 harboring peuR produced 1.86 and 1.79 times more peucemycin A (12.5 mg/L) and peucemycin B (21.5 mg/L), respectively, than the wild type. Finally, strain S. peucetius bldAR25 carrying bldA and peuR produced roughly 3.52 and 2.63 times more peucemycin A (23.8 mg/L) and peucemycin B (31.5 mg/L), respectively, than the wild type. Key points • This study identifies a new peucemycin derivative, 19-hydroxy peucemycin (peucemycin B). • The SARP regulator (PeuR) acts as a positive regulator of the peucemycin biosynthetic gene cluster. • The overexpression of peuR and heterologous expression of bldA increase the production of peucemycin derivatives.

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Section: Resultsmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A new peucemycin derivative and impacts of peuR and bldA on peucemycin biosynthesis in Streptomyces peucetius

Magar,

Pham,

Poudel

et al. 2024

Appl Microbiol Biotechnol

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“…Researchers modified the structure of quercetin so that it can be used in illness prevention and therapy as soon as possible. This involves altering hydroxyl groups to produce ethers and esters, adding substituents to the oxygen atom of carbonyl groups, and modifying the A and B rings [14,15] . Through optimization and modification, quercetin derivatives with good solubility, high bioavailability, obviously increased activity, and enhanced anticancer activity were developed.…”

Section: Introductionmentioning

confidence: 99%

Research Progress on Quercetin's Biological Activity and Structural Modification Based on Its Antitumor Effects

Guo,

Zeng,

Sun

et al. 2023

ChemistrySelect

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Quercetin is a naturally existing flavonoid with numerous physiological effects, including antitumor activity. It functions as an antitumor agent by inducing apoptosis and inhibiting tumor cell development, preventing tumor cell invasion and metastasis, and reversing tumor multidrug resistance. Quercetin has limited therapeutic usefulness due to its low water solubility, poor oral absorption, and low bioavailability. New quercetin derivatives are being developed and manufactured via a variety of methods to address inadequacies and for utilization in disease prevention and therapy. The synthesis and anticancer effects of quercetin derivatives, as well as the structure‐activity relationship of quercetin derivatives, were explored, and the unique dosage forms of these derivatives were summarized to serve as a reference for future quercetin research and development.

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The Probiotic Potential and Metabolite Characterization of Bioprotective Bacillus and Streptomyces for Applications in Animal Production

Evangelista,

Nazareth,

Luz

et al. 2024

Animals

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Probiotics are increasingly recognized for their potential in managing bacterial challenges in animal production. This study aimed to evaluate the probiotic potential of Bacillus and Streptomyces strains, specifically their bioprotective ability against Salmonella. In agar inhibition assays, these bacteria supported Salmonella-inhibition zones, ranging from 2.5 ± 0.5 to 6.3 ± 2.0 mm. Analyses of antimicrobial metabolites revealed their capacity to produce compounds with anti-Salmonella properties, except for Bacillus subtilis MLB2. When Salmonella was exposed to lyophilized metabolites, inhibition occurred in both liquid (at concentrations between 250 and 500 g/L) and solid cultures (at 500 g/L). To confirm their probiotic potential, the S. griseus and Bacillus strains underwent evaluations for antimicrobial resistance, bile salt tolerance, auto- and co-aggregation, pH resistance, and their ability to adhere to and inhibit Salmonella in Caco-2 cells. These assessments confirmed their probiotic potential. The probiotic strains were further encapsulated and subjected to simulated swine and poultry digestion. They demonstrated survival potential through the gastrointestinal tract and significantly reduced the Salmonella population. Thus, these strains exhibit considerable promise for producing biotechnological products aimed at controlling Salmonella in animal production. This approach ensures the health and hygiene of farming facilities, mitigates the spread of zoonotic bacteria, and contributes positively to public health.

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Biosynthetic pathway of peucemycin and identification of its derivative from Streptomyces peucetius

Cited by 3 publications

References 72 publications

A new peucemycin derivative and impacts of peuR and bldA on peucemycin biosynthesis in Streptomyces peucetius

A new peucemycin derivative and impacts of peuR and bldA on peucemycin biosynthesis in Streptomyces peucetius

Research Progress on Quercetin's Biological Activity and Structural Modification Based on Its Antitumor Effects

The Probiotic Potential and Metabolite Characterization of Bioprotective Bacillus and Streptomyces for Applications in Animal Production

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