Combinatorial biosynthesis and antibacterial evaluation of glycosylated derivatives of 12-membered macrolide antibiotic YC-17

Pramod B. Shinde; Ah Reum Han; Jaeyong Cho; So Ra Lee; Yeon Hee Ban; Young Ji Yoo; Eun Ji Kim; Eunji Kim; Myoung Chong Song; Je Won Park; Dong Gun Lee; Yeo Joon Yoon

doi:10.1016/j.jbiotec.2013.05.014

Combinatorial biosynthesis and antibacterial evaluation of glycosylated derivatives of 12-membered macrolide antibiotic YC-17

Pramod B. Shinde, Ah Reum Han, Jaeyong Cho, So Ra Lee, Yeon Hee Ban, Young Ji Yoo, Eun Ji Kim, Eunji Kim, Myoung Chong Song, Je Won Park, Dong Gun Lee, Yeo Joon Yoon

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

Expression plasmids carrying different deoxysugar biosynthetic gene cassettes and the gene encoding a substrate-flexible glycosyltransferase DesVII were constructed and introduced into Streptomyces venezuelae YJ003 mutant strain bearing a deletion of a desosamine biosynthetic (des) gene cluster. The resulting recombinants produced macrolide antibiotic YC-17 analogs possessing unnatural sugars replacing native d-desosamine. These metabolites were isolated and further purified using chromatographic techniques and their structures were determined as d-quinovosyl-10-deoxymethynolide, l-rhamnosyl-10-deoxymethynolide, l-olivosyl-10-deoxymethynolide, and d-boivinosyl-10-deoxymethynolide on the basis of 1D and 2D NMR and MS analyses and the stereochemistry of sugars was confirmed using coupling constant values and NOE correlations. Their antibacterial activities were evaluated in vitro against erythromycin-susceptible and -resistant Enterococcus faecium and Staphylococcus aureus. Substitution with l-rhamnose displayed better antibacterial activity than parent compound YC-17 containing native sugar d-desosamine. The present study on relationships between chemical structures and antibacterial activities could be useful in generation of novel advanced antibiotics utilizing combinatorial biosynthesis approach.

Original language	English
Pages (from-to)	142-148
Number of pages	7
Journal	Journal of Biotechnology
Volume	168
Issue number	2
DOIs	https://doi.org/10.1016/j.jbiotec.2013.05.014
Publication status	Published - 2013 Oct
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government Ministry of Education, Science and Technology (MEST) ( 20110018617 , 20110001340 , and 2011K000441 ); and the Intelligent Synthetic Biology Center of Global Frontier Project funded by the MEST ( 2011-0031961 ). This research was also supported by the Ewha Global Top5 Grant 2012 of Ewha Womans University . The bacterial strains were provided by the National Biobank of Korea – Kyungpook National University Hospital, which is supported by the Ministry of Health, Welfare and Family Affairs, and were obtained with informed consent under institutional review board-approved protocols.

Keywords

Combinatorial biosynthesis
Macrolides
Streptomyces venezuelae
YC-17

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology

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10.1016/j.jbiotec.2013.05.014

Cite this

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title = "Combinatorial biosynthesis and antibacterial evaluation of glycosylated derivatives of 12-membered macrolide antibiotic YC-17",

abstract = "Expression plasmids carrying different deoxysugar biosynthetic gene cassettes and the gene encoding a substrate-flexible glycosyltransferase DesVII were constructed and introduced into Streptomyces venezuelae YJ003 mutant strain bearing a deletion of a desosamine biosynthetic (des) gene cluster. The resulting recombinants produced macrolide antibiotic YC-17 analogs possessing unnatural sugars replacing native d-desosamine. These metabolites were isolated and further purified using chromatographic techniques and their structures were determined as d-quinovosyl-10-deoxymethynolide, l-rhamnosyl-10-deoxymethynolide, l-olivosyl-10-deoxymethynolide, and d-boivinosyl-10-deoxymethynolide on the basis of 1D and 2D NMR and MS analyses and the stereochemistry of sugars was confirmed using coupling constant values and NOE correlations. Their antibacterial activities were evaluated in vitro against erythromycin-susceptible and -resistant Enterococcus faecium and Staphylococcus aureus. Substitution with l-rhamnose displayed better antibacterial activity than parent compound YC-17 containing native sugar d-desosamine. The present study on relationships between chemical structures and antibacterial activities could be useful in generation of novel advanced antibiotics utilizing combinatorial biosynthesis approach.",

keywords = "Combinatorial biosynthesis, Macrolides, Streptomyces venezuelae, YC-17",

author = "Shinde, {Pramod B.} and Han, {Ah Reum} and Jaeyong Cho and Lee, {So Ra} and Ban, {Yeon Hee} and Yoo, {Young Ji} and Kim, {Eun Ji} and Eunji Kim and Song, {Myoung Chong} and Park, {Je Won} and Lee, {Dong Gun} and Yoon, {Yeo Joon}",

note = "Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government Ministry of Education, Science and Technology (MEST) ( 20110018617 , 20110001340 , and 2011K000441 ); and the Intelligent Synthetic Biology Center of Global Frontier Project funded by the MEST ( 2011-0031961 ). This research was also supported by the Ewha Global Top5 Grant 2012 of Ewha Womans University . The bacterial strains were provided by the National Biobank of Korea – Kyungpook National University Hospital, which is supported by the Ministry of Health, Welfare and Family Affairs, and were obtained with informed consent under institutional review board-approved protocols.",

year = "2013",

month = oct,

doi = "10.1016/j.jbiotec.2013.05.014",

language = "English",

volume = "168",

pages = "142--148",

journal = "Journal of Biotechnology",

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AU - Shinde, Pramod B.

AU - Han, Ah Reum

AU - Cho, Jaeyong

AU - Lee, So Ra

AU - Ban, Yeon Hee

AU - Yoo, Young Ji

AU - Kim, Eun Ji

AU - Kim, Eunji

AU - Song, Myoung Chong

AU - Park, Je Won

AU - Lee, Dong Gun

AU - Yoon, Yeo Joon

N1 - Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government Ministry of Education, Science and Technology (MEST) ( 20110018617 , 20110001340 , and 2011K000441 ); and the Intelligent Synthetic Biology Center of Global Frontier Project funded by the MEST ( 2011-0031961 ). This research was also supported by the Ewha Global Top5 Grant 2012 of Ewha Womans University . The bacterial strains were provided by the National Biobank of Korea – Kyungpook National University Hospital, which is supported by the Ministry of Health, Welfare and Family Affairs, and were obtained with informed consent under institutional review board-approved protocols.

PY - 2013/10

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N2 - Expression plasmids carrying different deoxysugar biosynthetic gene cassettes and the gene encoding a substrate-flexible glycosyltransferase DesVII were constructed and introduced into Streptomyces venezuelae YJ003 mutant strain bearing a deletion of a desosamine biosynthetic (des) gene cluster. The resulting recombinants produced macrolide antibiotic YC-17 analogs possessing unnatural sugars replacing native d-desosamine. These metabolites were isolated and further purified using chromatographic techniques and their structures were determined as d-quinovosyl-10-deoxymethynolide, l-rhamnosyl-10-deoxymethynolide, l-olivosyl-10-deoxymethynolide, and d-boivinosyl-10-deoxymethynolide on the basis of 1D and 2D NMR and MS analyses and the stereochemistry of sugars was confirmed using coupling constant values and NOE correlations. Their antibacterial activities were evaluated in vitro against erythromycin-susceptible and -resistant Enterococcus faecium and Staphylococcus aureus. Substitution with l-rhamnose displayed better antibacterial activity than parent compound YC-17 containing native sugar d-desosamine. The present study on relationships between chemical structures and antibacterial activities could be useful in generation of novel advanced antibiotics utilizing combinatorial biosynthesis approach.

AB - Expression plasmids carrying different deoxysugar biosynthetic gene cassettes and the gene encoding a substrate-flexible glycosyltransferase DesVII were constructed and introduced into Streptomyces venezuelae YJ003 mutant strain bearing a deletion of a desosamine biosynthetic (des) gene cluster. The resulting recombinants produced macrolide antibiotic YC-17 analogs possessing unnatural sugars replacing native d-desosamine. These metabolites were isolated and further purified using chromatographic techniques and their structures were determined as d-quinovosyl-10-deoxymethynolide, l-rhamnosyl-10-deoxymethynolide, l-olivosyl-10-deoxymethynolide, and d-boivinosyl-10-deoxymethynolide on the basis of 1D and 2D NMR and MS analyses and the stereochemistry of sugars was confirmed using coupling constant values and NOE correlations. Their antibacterial activities were evaluated in vitro against erythromycin-susceptible and -resistant Enterococcus faecium and Staphylococcus aureus. Substitution with l-rhamnose displayed better antibacterial activity than parent compound YC-17 containing native sugar d-desosamine. The present study on relationships between chemical structures and antibacterial activities could be useful in generation of novel advanced antibiotics utilizing combinatorial biosynthesis approach.

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KW - Macrolides

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SN - 0168-1656

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IS - 2

ER -

Combinatorial biosynthesis and antibacterial evaluation of glycosylated derivatives of 12-membered macrolide antibiotic YC-17

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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