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Metabolic Engineering of Nocardia sp. CS682 for Enhanced Production of Nargenicin A1

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Abstract

A number of secondary metabolites having therapeutic importance have been reported from the genus Nocardia. One of the polyketide antibiotic compounds isolated from Nocardia is nargenicin A1. Recently, nargenicin A1 has been isolated from Nocardia sp. CS682, a new Nocardia strain isolated from soil in Jeonnam, South Korea. It possesses strong antibacterial activity against methicillin-resistant Staphylococcus aureus. In this study, we applied a metabolic engineering approach based on recombinant DNA technology in order to boost the production of nargenicin A1 from Nocardia sp. CS682. Initially, we optimized the transformation of this new strain by electroporation method. Heterologous expression of S-adenosylmethionine synthetase (MetK1-sp) in Nocardia sp. CS682 enhanced the production of nargenicin A1 by about 2.8 times due to transcriptional activation of biosynthetic genes as revealed by reverse transcription polymerase chain reaction analysis. Similarly, expression of acetyl-CoA carboxylase genes improved nargenicin A1 production by about 3.8 times in Nocardia sp. ACC18 compared to that in Nocardia sp. CS682 and Nocardia sp. NV18 by increasing precursor pool. Thus, enhanced production of nargenicin A1 from Nocardia sp. CS682 can be achieved by expression of transcriptional activator genes and precursor genes from Streptomyces strains.

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Acknowledgments

This study was supported by the Technology Development Program for Agriculture and Forestry, Ministry of Agriculture and Forestry (20100368), Republic of Korea, 2010 and by the National Research Foundation of Korea (the Global Frontier Program for the Intelligent Synthetic Biology). We are grateful to Professor Kazuhiro Chiba for providing Nocardia–E. coli shuttle vectors, pNV18 and pNV19.

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Authors and Affiliations

  1. Institute of Biomolecule Reconstruction, Sun Moon University, 100, Kalsan-ri, Tangjeonmyun, Asansi, Chungnam, 336-708, Republic of Korea

    Sushila Maharjan, Dinesh Koju, Hei Chan Lee & Jae Kyung Sohng

  2. Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, 501-759, South Korea

    ** Cheol Yoo

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  1. Sushila Maharjan
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  2. Dinesh Koju
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  3. Hei Chan Lee
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  4. ** Cheol Yoo
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  5. Jae Kyung Sohng
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Correspondence to Jae Kyung Sohng.

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Maharjan, S., Koju, D., Lee, H.C. et al. Metabolic Engineering of Nocardia sp. CS682 for Enhanced Production of Nargenicin A1 . Appl Biochem Biotechnol 166, 805–817 (2012). https://doi.org/10.1007/s12010-011-9470-1

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