Microbial Biosynthesis of Chrysazin Derivatives in Recombinant Escherichia coli and Their Biological Activities

Poudel, Purna Bahadur; Dhakal, Dipesh; Magar, Rubin Thapa; Sohng, Jae Kyung

doi:10.3390/molecules27175554

Cited by 10 publications

(3 citation statements)

References 34 publications

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“…The compound dissolved in DMSO was used for the test along with DMSO as a negative control and erythromycin as a positive control. The antibacterial effect was assessed after incubating plates at 37 °C for 16 − 24 h (Weinstein et al 2018 ; Poudel et al 2022 ).…”

Section: Methodsmentioning

confidence: 99%

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: Methodsmentioning

confidence: 99%

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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“…(Figure 5). [101] Biosynthesized chrysazin‐8‐ O ‐α‐l‐rhamnoside 87 and chrysazin‐8‐ O ‐α‐l‐2’‐ O ‐methylrhamnoside 88 exhibited a very good potency against MRSA [102] …”

Section: Antibacterial Activity Of Anthraquinonesmentioning

confidence: 99%

Exploring Anthraquinones as Antibacterial and Antifungal agents

et al. 2023

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Anthraquinones having an anthracene core structure with two carbonyl groups are essential compounds in therapeutic applications. One of the growing concerns within the medical community is antimicrobial resistance. Multiple drug-resistant microbes can worsen a disease that can be easily treated with normal drugs. Microbes also produce biofilms that further enhance their resistance to antimicrobials, rendering biofilm-associated infections challenging to eradicate. This review provides an update on the antibacterial and antifungal activities of natural and synthetic anthraquinone derivatives. The mechanism of antibacterial and antifungal action of anthraquinones are summarised, which will help in designing new therapeutically effective anthraquinone compounds.

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“…Polyketides are a diverse family of natural products that display a vast array of biological activities, including antimicrobial, antiparasitic, antifungal, and anticancer properties. They have also various commercial applications as food additives, nutraceuticals, and pigments [4][5][6][7][8][9][10]. The synthesis of most polyketides involves the use of three main classes of PKSs, namely type I PKS, type II PKS, and type III PKS.…”

Section: Introductionmentioning

confidence: 99%

Identification of 1,3,6,8-Tetrahydroxynaphthalene Synthase (ThnA) from Nocardia sp. CS682

Poudel

Magar

Bridget

et al. 2023

J. Microbiol. Biotechnol.

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Type III polyketide synthase (PKS) found in bacteria is known as 1,3,6,8-tetrahydroxynaphthalene synthase (THNS). Microbial type III PKSs synthesize various compounds that possess crucial biological functions and significant pharmaceutical activities. Based on our sequence analysis, we have identified a putative type III polyketide synthase from Nocardia sp. CS682 was named as ThnA. The role of ThnA, in Nocardia sp. CS682 during the biosynthesis of 1,3,6,8 tetrahydroxynaphthalene (THN), which is the key intermediate of 1-( α -L-(2- O -methyl)-6-deoxymannopyranosyloxy)-3,6,8-trimethoxynaphthalene (IBR-3) was characterized. ThnA utilized five molecules of malonyl-CoA as a starter substrate to generate the polyketide 1,3,6,8-tetrahydroxynaphthalene, which could spontaneously be oxidized to the red flaviolin compound 2,5,7-trihydroxy-1,4-naphthoquinone. The amino acid sequence alignment of ThnA revealed similarities with a previously identified type III PKS and identified Cys 138 , Phe 188 , His 270 , and Asn 303 as four highly conserved active site amino acid residues, as found in other known polyketide synthases. In this study, we report the heterologous expression of the type III polyketide synthase thnA in S. lividan TK24 and the identification of THN production in a mutant strain. We also compared the transcription level of thnA in S. lividan TK24 and S. lividan pIBR25- thnA and found that thnA was only transcribed in the mutant.

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Microbial Biosynthesis of Chrysazin Derivatives in Recombinant Escherichia coli and Their Biological Activities

Cited by 10 publications

References 34 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

Exploring Anthraquinones as Antibacterial and Antifungal agents

Identification of 1,3,6,8-Tetrahydroxynaphthalene Synthase (ThnA) from Nocardia sp. CS682

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