title: Enhancement of dalesconols A and B production via upregulation of laccase activity by medium optimization and inducer supplementation in submerged fermentation of Daldinia eschscholzii.
abstract: Dalesconols (dalesconols A and B) are novel polyketides with strong immunosuppressive activity produced by Daldinia eschscholzii. In this work, the effects of different media (M1, M2, and M3) on fungus growth and dalesconols biosynthesis were firstly tested and compared. Intermediates and enzyme analysis indicated that laccase had the major contribution to dalesconols biosynthesis. The key role of laccase on dalesconols biosynthesis was further experimentally confirmed, which suggested that the modified M2 was more favored for laccase and dalesconols production. Thereafter, the medium composition was optimized by RSM with a fermentation titer of 36.66 mg/L obtained. Furthermore, Ca(2+) induction was employed to up-regulate of laccase activity and further enhanced dalesconols production (76.90 mg/L), which was 308% higher than that in M2. In addition, dalesconols production reached 63.42 mg/L in scale-up experiments. This work indicated great potential of laccase as a key enzyme on regulation of dalesconols production.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, PR China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai 200237, PR China.
authors.forename: Zheng-Hua
authors.initials: ZH
authors.lastname: Pan
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, PR China.
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Jiao
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, PR China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai 200237, PR China. Electronic address: luyanhua@ecust.edu.cn.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Lu
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, PR China.
authors.forename: Ren-Xiang
authors.initials: RX
authors.lastname: Tan
mesh_terms: D019149:Bioreactors; D002118:Calcium / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D005285:Fermentation; D007218:Industrial Microbiology / Q000295:instrumentation / Q000379:methods*; D042845:Laccase / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D015854:Up-Regulation; D013098:Xylariales / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
chemical_list: D003470:Culture Media; D011084:Polycyclic Aromatic Hydrocarbons; C552720:dalesconol A; C552721:dalesconol B; D002244:Carbon; D042845:Laccase; D009584:Nitrogen; D002118:Calcium
keywords: Daldinia eschscholzii; Dalesconols A; Dalesconols B; Laccase activity; Submerged fermentation