Development of a high-yielding bioprocess for 11-α hydroxylation of canrenone under conditions of oxygen-enriched air supply.
A high yielding bioprocess for 11-α hydroxylation of canrenone (1a) using Aspergillus ochraceus ATCC 18500 was developed. The optimization of the biotransformation involved both fermentation (for achieving highly active mycelium of A. ochraceus) and biotransformation with the aim to obtain 11-α hydroxylation with high selectivity and yield. A medium based on sucrose as C-source resulted particularly suitable for conversion of canrenone into the corresponding 11-hydroxy derivative, whereas the use of O2-enriched air and dimethyl sulfoxide (DMSO) as a co-solvent for increasing substrate solubility played a crucial role for obtaining high yields (>95%) of the desired product in high chemical purity starting from 30mM (10.2g/L) of substrate. The structure of the hydroxylated product was confirmed by a combination of two-dimensional NMR proton-proton correlation techniques.
Department of Food, Environmental and Nutritional Science (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.
Martina Letizia
ML
Contente
Department of Medical Biotechnology and Translational Medicine, University of Milan, Via Saldini 50, 20133 Milan, Italy.
Benedetta
B
Guidi
Department of Food, Environmental and Nutritional Science (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.
Immacolata
I
Serra
Department of Food, Environmental and Nutritional Science (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.
Valerio
V
De Vitis
Department of Food, Environmental and Nutritional Science (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.
Diego
D
Romano
Department of Pharmaceutical Sciences (DISFARM), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.
Andrea
A
Pinto
Industriale Chimica, Via Grieg 13, 21047 Saronno (VA), Italy.
Roberto
R
Lenna
Biochemical and Pharmaceutical Technology Department, Faculty of Pharmaceutical Sciences, University of São Paulo, Av Professor Lineu Prestes 580, São Paulo 05508-900, Brazil.
Ricardo Pinheiro
RP
de Souza Oliveira
Department of Food, Environmental and Nutritional Science (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy. Electronic address: francesco.molinari@unimi.it.
Francesco
F
Molinari
D001235:Aspergillus ochraceus / Q000378:metabolism; D055162:Biocatalysis; D001711:Biotransformation; D002192:Canrenone / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*
D002192:Canrenone; D006899:Mixed Function Oxygenases; D010100:Oxygen
Aspergillus ochraceus; Biocatalysis; Biotransformation; Canrenone; Monooxygenase; Steroid hydroxylation