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http://dx.doi.org/10.4014/jmb.1202.02027

Effect of Different Biosynthetic Precursors on the Production of Nargenicin $A_1$ from Metabolically Engineered Nocardia sp. CS682  

Koju, Dinesh (Institute of Biomolecule Reconstruction, Sun Moon University)
Maharjan, Sushila (Institute of Biomolecule Reconstruction, Sun Moon University)
Dhakal, Dipesh (Institute of Biomolecule Reconstruction, Sun Moon University)
Yoo, Jin Cheol (Department of Pharmacy, College of Pharmacy, Chosun University)
Sohng, Jae Kyung (Institute of Biomolecule Reconstruction, Sun Moon University)
Publication Information
Journal of Microbiology and Biotechnology / v.22, no.8, 2012 , pp. 1127-1132 More about this Journal
Abstract
Nargenicin $A_1$ is a 28-membered polyketide macrolide, with antibacterial activity against methicillin-resistant Staphylococcus aureus, produced by Nocardia sp. CS682. In this study, the production of nargenicin $A_1$ was improved by enhancing the supply of different biosynthetic precursors. In Nocardia sp. CS682 (KCTC11297BP), this improvement was ~4.62-fold with the supplementation of 30 mM methyl oleate, 4.25-fold with supplementation of 15mM sodium propionate, and 2.81-fold with supplementation of 15 mM sodium acetate. In Nocardia sp. metK18 and Nocardia sp. CS682 expressing S-adenosylmethionine synthetase (MetK), the production of nargenicin $A_1$ was improved by ~5.57-fold by supplementation with 30 mM methyl oleate, 5.01-fold by supplementation with 15 mM sodium propionate, and 3.64-fold by supplementation with 15 mM sodium acetate. Furthermore, supplementing the culture broth of Nocardia sp. ACC18 and Nocardia sp. CS682 expressing the acetyl-CoA carboxylase complex (AccA2 and AccBE) with 30 mM methyl oleate, 15 mM sodium propionate, or 15 mM sodium acetate resulted in ~6.99-, 6.46-, and 5.58-fold increases, respectively, in nargenicin $A_1$ production. Our overall results showed that among the supplements, methyl oleate was the most effective precursor supporting the highest titers of nargenicin $A_1$ in Nocardia sp. CS682, Nocardia sp. metK18, and Nocardia sp. ACC18.
Keywords
Methyl oleate; Nocardia sp. CS682; nargenicin $A_1$; polyketide; precursor;
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