title: Enhancement of microbial hydroxylation of 13-ethyl-gon-4-ene-3,17-dione by Metarhizium anisopliae using nano-liposome technique.
abstract: The introduction of 11α-hydroxy to 13-ethyl-gon-4-ene-3,17-dione (GD) by microbial transformation is a key step in the synthesis of oral contraceptive desogestrel, while low substrate solubility and uptake into cells are tough problems influencing biotransformation efficiency greatly. Nano-liposome technique was used in the hydroxylation of GD by Metarhizium anisopliae. The substrate GD was processed to be GD-loaded nano-liposomes (GNLs) with high stability and encapsulation efficiency, and then applied in microbial hydroxylation by M. anisopliae. The results proved that the yield of the main product 11α-hydroxy-13-ethyl-gon-4-ene-3,17-dione (HGD) tripled compared to regular solvent dimethylformamide dispersion method at 2 g/l of substrate feeding concentration, and the HGD conversion rate showed no obvious reduction when the substrate feeding concentration increased from 2 to 6 g/l, which indicated the improvement of GNL addition method on biotransformation. Furthermore, the main byproduct changed from 6β-hydroxy derivative of GD (with similar polarity to HGD) to 6β,11α-dihydroxy derivative, which benefits the following purification of HGD from fermentation broth. These advantages suggest a great potential for the application of nano-liposome technique in microbial steroid transformation.
authors.affiliation: Department of Biosynthesis, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Feng
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Liao
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Jiyang
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Ye
mesh_terms: D001711:Biotransformation; D005285:Fermentation; D006067:Gonanes / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation; D008081:Liposomes / Q000737:chemistry* / Q000648:ultrastructure; D052981:Metarhizium / Q000378:metabolism*; D049329:Nanostructures / Q000648:ultrastructure; D036103:Nanotechnology; D012995:Solubility
chemical_list: D006067:Gonanes; D008081:Liposomes; C055308:13-ethyl-gon-4-ene-3,17-dione