Journal of Applied Sciences Research, 3(10): 921-925, 2007
© 2007, INSInet Publication
Corresponding Author: I.S. Abd-Elsalam, Department of Natural and Microbial products chem.
921
Factorial Design for the Production of Some Steroidal Hormones from Sunflower Oil
Sterols by Fusarium solani
I.S. Abd-Elsalam, H.A. El-Refai and A.M. Abouel-Fotouh
1 1 2
Department of Natural and Microbial products chem.
1
Department of Mech. Eng. (National research center)
2
Abstract: The bioconversion of plant sterols (phytosterols) by Fusarium solani to produce some C-19
androstene steroids namely androstenedione (AD) and androstadienedione (ADD) has been investigated. The
purpose of this study was to determine the conditions for maximum yields of both AD and ADD using factorial
design and multi-dimensional response surface (RSM) modeling techniques. Therefore, the effect of three
factors (pH, biotransformation time and substrate level on the yields of both AD and ADD were assessed using
a sequential factorial design. The results indicated that the biotransformation time was critical for the production
of AD and ADD, while the pH value of the fermentation medium affected the yield of both AD and ADD to
a lesser extent. An optimization experiment was performed using factor levels within narrower range of the
setting determined from the first experiment, the yield of AD and ADD predicted by the mathematical model
increased to 65.71 and 20.41 %, respectively and this value were confirmed experimentally.
Key words: Bioconversion, Sunflower sterols, Factorial design, Androstene, Steroid.
INTRODUCTION
Although the steroid drugs represent only a small part
of the world market of pharmaceuticals, there is a great
demand for new and cheaper steroid raw materials for
their production . The choice of starting materials has
[2,5,3,4]
always had a critical, impact on steroid manufacturing
industries. The most common and economical process, for
the production of steroid pharmaceuticals is the partial
synthesis from relatively inexpensive steroid row
materials of animal and plant origins.
One of the most important bioconversion reaction of
steroid is the side chain degradation of sterols specially,
cholesterol. b-sitosterol,which had been studied . The
[7,12]
biodegredation products were the highly active steroidal
hormones AD and ADD, which are important
intermediates in the production of estrone and estradiol.
There are different strains which have the ability to
degrade phytosterols. The highly active strains were
Fusarium spp, Aspergillus spp. in addition to some
bacterial strains. The studies of El- Refai and Abd-
Elsalam , stated that the strain of F. solni has the ability
[6]
to transform â- sitosterol, as well as sun flower sterols
mixture to gave a good yields of both AD, ADD. The
work was extended in this communication to build a
mathematical design for optimizing the bioconversion
19
process in favour of the desired C androgenes.
MATERIALS AND METHODS
Materials:
Microorganisms: Fusarium solani was kindly provided
from the Natural and Microbial Products Chemistry
Department, National Research Centre (NRC) Dokki,
Cairo, Egypt.
Chemicals: The authentic steroids used (AD, ADD,
â-sitosterol), and 8-hydroxyquinoline were provided by of
Sigma Company USA. Sunflower oil used in the current
work is of commercial grade.
Methods:
Maintenance of the Microorganism: The experimental
organism was maintained on the following medium g/l
(malt extract 25, yeast extract 4 and agar 20) and was
monthly interval regenerated.
Transformation process: Cultivation was performed
using 250 ml Erlenmeyer flasks, each containing 50 ml of
4 2 4
the following medium (g/l): glucose, 10; (NH ) SO , 1.0,
2 4 2 4
K HPO , 7.0; KH P0 ,3.0. To each flask 0.016 g/1 8-
hydroxyquinoline was added to avoid the enzymatic
cission of the sterol nucleus . The pH was adjusted to
[8]
6.5. The flasks were sterilized using steam autoclaving at
120 C for 20 min and incubated with 2 ml spore
o
suspension of F. solani 7 days old culture. The culture
flasks were agitated on reciprocal shaker (200 rpm) at
30°C±for 72h . Thereafter, the sunflower sterols mixture
(5 mg) was added to each flask and the transformation
process was continued for the specific time intervals .
[6]
Extraction: At the end of the transformation period, the
content of each flask was homogenized in a blender
(16000 rpm) with double its volume of chloroform. The
chloroform layer was separated and dried under vacuum
to give semi-solid residue "test material".