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Biotransformation of Rosamicin Antibiotic into 10,11-Dihydrorosamicin with Enhanced In Vitro Antibacterial Activity Against MRSA
Biotransformation of Rosamicin Antibiotic into 10,11-Dihydrorosamicin with Enhanced In Vitro Antibacterial Activity Against MRSA
Journal of Microbiology and Biotechnology. 2014. Jan, 24(1): 44-47
Copyright © 2014, The Korean Society For Microbiology And Biotechnology
  • Received : June 24, 2013
  • Accepted : September 23, 2013
  • Published : January 28, 2014
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About the Authors
Nguyen Lan Huong
Department of Pharmaceutical Engineering, SunMoon University, Asan 336-708, Republic of Korea
Nguyen Huu Hoang
Department of Pharmaceutical Engineering, SunMoon University, Asan 336-708, Republic of Korea
Anil Shrestha
Department of Pharmaceutical Engineering, SunMoon University, Asan 336-708, Republic of Korea
Jae Kyung Sohng
Department of Pharmaceutical Engineering, SunMoon University, Asan 336-708, Republic of Korea
Yeo Joon Yoon
Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Republic of Korea
Je Won Park
Department of Pharmaceutical Engineering, SunMoon University, Asan 336-708, Republic of Korea
jepark@sunmoon.ac.kr

Abstract
A biotransformation approach using microbes as biocatalysts can be an efficient tool for the targeted modification of existing antibiotic chemical scaffolds to create previously uncharacterized therapeutic agents. By employing a recombinant Streptomyces venezuelae strain as a microbial catalyst, a reduced macrolide, 10,11-dihydrorosamicin, was created from rosamicin macrolide. Its chemical structure was spectroscopically elucidated, and the new rosamicin analog showed 2-4-fold higher antibacterial activity against two strains of methicillin-resistant Staphylococcus aureus compared with its parent rosamicin. This kind of biocatalytic approach is able to expand existing antibiotic entities and can also provide more diverse therapeutic resources.
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Acknowledgements
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea Ministry of Education, Science and Technology (MEST) (20122039424), the Intelligent Synthetic Biology Center of Global Frontier Project (20128054880) funded by MEST, and by grants (JWP: PJ0094834 and JKS: PJ0094832) funded by the Next Generation BioGreen21 program, Rural Development Administration.
References
Anzai Y , Iizaka Y , Li W , Idemoto N , Tsukada S , Koike K 2009 Production of rosamicin derivatives in Micromonospora rosaria by introduction of D-mycinose biosynthetic gene with PhiC31-derived integration vector pSET152. J. Ind. Microbiol. Biotechnol. 36 1013 - 1021    DOI : 10.1007/s10295-009-0579-y
Anzai Y , Sakai A , Li W , Iizaka Y , Koike K , Kinoshita K , Kato F 2010 Isolation and characterization of 23-Omycinosyl- 20-dihydro-rosamicin: a new rosamicin analogue derived from engineered Micromonospora rosaria. J. Antibiot. 63 325 - 328    DOI : 10.1038/ja.2010.38
Baumueller A , Hoyme U , Madsen PO 1977 Rosamicin – a new drug for the treatment of bacterial prostatitis. Antimicrob. Agents Chemother. 12 240 - 242    DOI : 10.1128/AAC.12.2.240
Fischbach MA , Walsh CT 2009 Antibiotics for emerging pathogens. Science 325 1089 - 1093    DOI : 10.1126/science.1176667
Iizaka Y , Higashi N , Ishida M , Oiwa R , Ichikawa Y , Takeda M 2013 Function of cytochrome P450 enzymes RosC and RosD in the biosynthesis of rosamicin macrolide antibiotic produced by Micromonospora rosaria. Antimicrob. Agents Chemother. 57 1529 - 1531    DOI : 10.1128/AAC.02092-12
Lee BK , Puar MS , Patel M , Bartner P , Lotvin J , Munayyer H , Waitz JA 1983 Multistep bioconversion of 20-deoxo-20-dihydro-12,13-deepoxy-12,13-dehydrorosaranolide to 22-hydroxy-23-O-mycinosyl-20-deoxo-20-dihydro-12,13-deepoxy-rosaramicin. J. Antibiot. 36 742 - 744    DOI : 10.7164/antibiotics.36.742
Park JW , Oh HS , Jung WS , Park SR , Han AR , Ban YH 2008 Exploiting the natural metabolic diversity of Streptomyces venezuelae to generate unusual reduced macrolides. Chem. Commun. 44 5782 - 5784    DOI : 10.1039/b814603a
Park JW , Park SR , Han AR , Ban YH , Yoo YJ , Kim EJ 2011 Generation of reduced macrolide analogs by regiospecific biotransformation. J. Antibiot. 64 155 - 157    DOI : 10.1038/ja.2010.143
Park JW , Park SR , Han AR , Ban YH , Yoo YJ , Kim EJ 2011 Microbial transformation of trichostatin A to 2,3-dihydrotrichostatin A. J. Nat. Prod. 74 1272 - 1274    DOI : 10.1021/np1006718
Park JW , Park SR , Nepal KK , Han AR , Ban YH , Yoo YJ 2011 Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation. Nat. Chem. Biol. 7 843 - 852    DOI : 10.1038/nchembio.671
Sadakane N , Tanaka Y , Omura S 1982 Hybrid biosynthesis of derivatives of protylonolide and M-4365 by macrolideproducing microorganisms. J. Antibiot. 35 680 - 687    DOI : 10.7164/antibiotics.35.680
Saleem M , Nazir M , Ali MS , Hussain H , Lee YS , Riaz N , Jabbar A 2010 Antimicrobial natural products: an update on future antibiotic drug candidates. Nat. Prod. Rep. 27 238 - 254    DOI : 10.1039/b916096e
Wagman GH , Waitz JA , Marquez J , Murawaski A , Oden EM , Testa RT , Weinstein MJ 1972 A new Micromonosporaproduced macrolide antibiotic, rosamicin. J. Antibiot. 25 641 - 646    DOI : 10.7164/antibiotics.25.641
Zhou J , Ogle JW , Fan Y , Banphavichit V , Zhu Y , Burgess K 2007 Asymmetric hydrogenation routes to deoxypolyketide chirons. Chemistry 13 7162 - 7170    DOI : 10.1002/chem.200700390