Effects of Impeller Geometry on the 11α-Hydroxylation of Canrenone in Rushton Turbine-Stirred Tanks

Abstract

The steroid compound 11α-hydroxycanrenone is an important intermediate for the synthesis of the antihypertensive drug eplerenone, which can be obtained by 11α-hydroxylation of canrenone [1]. Studies have revealed that biotransformation is a common method for the synthesis of steroid hormone drug intermediates [2,3]. For example, Aspergillus spp. and Rhizopus spp. are frequently used for the 11α-hydroxylation of canrenone, in which cytochromes P450 (P450s) are the key to bioconversion [4,5]. P450s belong to the group of external monooxygenases, and the supply of oxygen is the basic requirement for the 11α-hydroxylation of canrenone [6].It is known that aerobic fermentation is affected by the type and geometry of the impeller in stirred tanks [7][8][9]. The gas dispersion, flow pattern and mixing in bioreactors are all affected by these factors. The gas distribution has a great influence on the dissolved oxygen (DO) content in fermentation broth [10,11]. Shin et al. indicated that the oxygen supply of fermentation broth, which was the restrictive factor for enzyme production by Aspergillus oryzae, was affected by impeller geometries [12]. The growth of microorganisms and the expression of enzymes in fermentation were also affected by DO [13,14]. Regarding the flow pattern and mixing, it is known that in submerged fermentation, the product quality is affected by these factors [15,16]. Li et al. found that mixing was improved by increasing the impeller diameter by approximately 10% in the enzyme production of A. oryzae fermentation [17]. In the nemadectin fermentation process, Wang et al. found that the radial-axial impeller combination with a time average velocity of 0.38-0.54 U tip was more beneficial for the activity of Streptomyces cyaneogriseus ssp. noncyanogenus and nemadectin biosynthesis than other combinations [18].In addition, the properties of the fermentation broth and microbial morphology, which greatly influence fermentation, are affected by the impeller type [19,20]. Li et al. showed that the hyphal morphology was related to the hydrodynamic stress and hyphal tensile strength [21]. There is also a correlation between the hydrodynamic stresses and impeller types. Ghobadi et al. increased the pellet porosity during mixing via a flexible shaft agitator, The 11α-hydroxylation of canrenone can be catalyzed by Aspergillus ochraceus in bioreactors, where the geometry of the impeller greatly influences the biotransformation. In this study, the effects of the blade number and impeller diameter of a Rushton turbine on the 11α-hydroxylation of canrenone were considered. The results of fermentation experiments using a 50 mm four-blade impeller showed that 3.40% and 11.43% increases in the conversion ratio were achieved by increasing the blade number and impeller diameter, respectively. However, with an impeller diameter of 60 mm, the conversion ratio with a six-blade impeller was 14.42% lower than that with a four-blade impeller. Data from cold model experiments with a large-diameter six-blade impeller indicated t...

Biotransformation of Ursonic Acid by Aspergillus ochraceus and Aspergillus oryzae to Discover Anti-Neuroinflammatory Derivatives

“…A. ochraceus is prevalently found in the environment, commonly in soil and decaying plant matter. Historically, A. ochraceus has been employed as a biocatalyst in the hydroxylation processes of steroids, triterpenes, flavonoids, and coumarins [34][35][36][37]. In our present investigation, we discerned that A. ochraceus primarily initiated hydroxylation, oxidation, lactonization, and epoxidation reactions on UNA.…”