Identification and enhancing production of a novel macrolide compound in engineered<i>Streptomyces peucetius</i>

Pham, Van Thuy Thi; Nguyen, Hue Thi; Nguyen, Chung Thanh; Choi, Ye Seul; Dhakal, Dipesh; Kim, Taesu; Jung, Hye Jin; Yamaguchi, Tokutaro; Sohng, Jae Kyung

doi:10.1039/d0ra06099b

Cited by 7 publications

(6 citation statements)

References 51 publications

(61 reference statements)

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“…S3 . Compared to the structure of peucemycin (Pham et al 2021 ), a chemical shift (δ C ) of C-19 from 21.24 ppm of peucemycin to 62.89 ppm of peucemycin B was found. Similarly, a chemical shift (δ C ) of C-20 from 14.01 ppm of peucemycin to 24.35 ppm of peucemycin B was found.…”

Section: Resultsmentioning

confidence: 69%

“…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: 70%

“…Streptomyces peucetius produces a number of bioactive secondary metabolites including daunorubicin (DNR), doxorubicin (DXR) (Arcamone and Cassinelli 1998 ; Arcamone et al 1969 ), flaviolin (Ghimire et al 2008 ), geosmin (Singh et al 2009 ), peucechelin (Park et al 2013 ) (Kodani et al 2015 ), and hopene (Ghimire et al 2015 ). Furthermore, a new 14-membered macrolide (peucemycin) with a γ-pyrone ring was purified and assigned its structure (Pham et al 2021 ). The compound exhibited antibacterial activities against some pathogens and suppressed the viability of various cancer cell lines (Pham et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, a new 14-membered macrolide (peucemycin) with a γ-pyrone ring was purified and assigned its structure (Pham et al 2021 ). 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 ).…”

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: Resultsmentioning

confidence: 70%

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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“…15 Doxorubicin from S. peucetius induces oxidative stress by releasing reactive oxygen species, thereby damaging DNA and triggering apoptosis in cancer cells. 16 Maculosin, a promising antioxidant molecule produced by Streptomyces sp. KTM 18, is used to treat deoxygenation in atherosclerosis, as well as neurodegenerative and inflammatory diseases.…”

mentioning

confidence: 99%

Evaluation of Mangrove Soil Streptomyces spp. Exhibiting Culture and Biochemical Variation for Determination of Antibacterial Activity

Akshatha¹,

Kalyani²

2022

J. Pure Appl. Microbiol.

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Among actinobacteria, the genus Streptomyces are found in abundance in specific soil environments. Streptomyces are cultivable using Streptomyces-specific media, including starch casein, yeast extract, or ISP 2 media. Streptomyces isolates can be identified based on their macroscopic culture morphology and microscopic observations, and can be taxonomically placed within the Streptomyces genus. In the present study, mangrove soil samples collected from the coast of Mangalore harboring a multitude of microorganisms were enriched with calcium carbonate and pre-heated to isolate Streptomyces organisms. Cultures were quantified in colony forming units and their diversity was evaluated based on phenotypic features, enzyme hydrolysis, biochemical testing, and antibiotic sensitivity tests. The cross streaking method was used to select Streptomyces isolates, which were then further subjected to intracellular buffer extraction and evaluated against test organisms to determine their antibacterial efficacy. This study highlights the occurrence of prominent Streptomyces species with effective antibacterial activity in a unique environmental habitat of mangrove soil on the Mangalore coast.

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Biotechnological and industrial applications of Streptomyces metabolites

Khushboo

Kumar

Dubey

et al. 2021

Biofuels Bioprod Bioref

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Streptomyces sp. produces clinically important bioactive compounds with anticancer, antiviral, and antibacterial properties. These compounds have important roles in various fields like agriculture, and medicine, with bio-economic benefits. Progress in genome mining has resulted in the characterization of various secondary metabolites such as lipstatin, macrolide lactones, clavulanic acid, and cholesterol oxidase. Integration of DNA sequencing with computational tools has provided information regarding the biosynthetic pathways of secondary metabolites. This information is leading to the modulation of associated metabolic pathways to expand the biotechnological and industrial applications of metabolites. The increased utilization of bioactive compounds requires sustainable production to improve the bioeconomy. In this review, the authors discuss the bioactive compounds isolated from Streptomyces and advanced approaches to improve their production.

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Identification and enhancing production of a novel macrolide compound in engineeredStreptomyces peucetius

Abstract: Activation of peucemycin in S. peucetius DM07 by the OSMAC strategy.

Cited by 7 publications

References 51 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

Evaluation of Mangrove Soil Streptomyces spp. Exhibiting Culture and Biochemical Variation for Determination of Antibacterial Activity

Biotechnological and industrial applications of Streptomyces metabolites

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