Effect of different biosynthetic precursors on the production of nargenicin A1 from metabolically engineered Nocardia sp. CS682.
Nargenicin A1 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 A1 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 15 mM 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 A1 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 A1 production. Our overall results showed that among the supplements, methyl oleate was the most effective precursor supporting the highest titers of nargenicin A1 in Nocardia sp. CS682, Nocardia sp. metK18, and Nocardia sp. ACC18.
Institute of Biomolecule Reconstruction, Sun Moon University, 100 Kalsan-ri, Tangjeonmyun, Asansi 336-708, Korea.
Dinesh
D
Koju
Sushila
S
Maharjan
Dipesh
D
Dhakal
Jin Cheol
JC
Yoo
Jae Kyung
JK
Sohng
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D053898:Biosynthetic Pathways / Q000235:genetics*; D003470:Culture Media / Q000737:chemistry; D007783:Lactones / Q000378:metabolism; D060847:Metabolic Engineering; D009615:Nocardia / Q000235:genetics* / Q000378:metabolism*; D009829:Oleic Acids / Q000378:metabolism; D011422:Propionates / Q000378:metabolism; D019346:Sodium Acetate / Q000378:metabolism
D000900:Anti-Bacterial Agents; D003470:Culture Media; D007783:Lactones; D009829:Oleic Acids; D011422:Propionates; C005576:methyl oleate; D019346:Sodium Acetate; C034624:nargenicin A1; C514135:sodium propionate