title: Enhanced production of squalene in the thraustochytrid Aurantiochytrium mangrovei by medium optimization and treatment with terbinafine.
abstract: Squalene is an effective chemopreventive agent in reducing the incident of coronary heart disease and cancer. It is also a strong antioxidant used extensively in the food and cosmetic industries. Microbial sources of squalene are being explored in recent years. The objective of this study is to increase the squalene content and yield in the thraustochytrid, Aurantiochytrium mangrovei FB3 through medium optimization and the treatment with terbinafine, an inhibitor of squalene monooxygenase in the sterol biosynthetic pathway. The highest biomass concentration of 21.2 g l(-1) was obtained at a glucose concentration of 60 g l(-1), while the highest specific growth rate of 0.077 h(-1) and the growth yield coefficient of 0.44 g g(-1) based on glucose were achieved at a lower glucose concentration (30 g l(-1)). The addition of terbinafine led to a slight inhibition of cell growth whereas an obvious increase in squalene content was observed at terbinafine concentrations of 10 and 100 mg l(-1), which corresponded to an increase of 36 and 40% in squalene content, respectively compared to the control. The addition of terbinafine was thus effective in inducing the accumulation of squalene in A. mangrovei. This study not only demonstrated the production potential of squalene by A. mangrovei, but also provided novel information on the accumulation effect of terbinafine on the biosynthesis of an essential intermediate involved in sterol metabolic pathway.
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong.
authors.forename: King Wai
authors.initials: KW
authors.lastname: Fan
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Aki
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
references.citation: J Agric Food Chem. 2009 May 27;57(10):4267-72
references.pmid: 19371138
references.citation: J Agric Food Chem. 2002 Jan 16;50(2):368-72
references.pmid: 11782209
references.citation: Expert Opin Investig Drugs. 2000 Aug;9(8):1841-8
references.pmid: 11060781
references.citation: J Agric Food Chem. 2007 Apr 18;55(8):2906-10
references.pmid: 17381126
references.citation: Ann N Y Acad Sci. 1999;889:193-203
references.pmid: 10668494
references.citation: Altern Med Rev. 1999 Feb;4(1):29-36
references.pmid: 9988781
references.citation: J Agric Food Chem. 2004 Mar 10;52(5):1196-200
references.pmid: 14995120
references.citation: Biochem Biophys Res Commun. 2002 Apr 19;292(5):1283-8
references.pmid: 11969229
references.citation: Mar Biotechnol (NY). 2001 Sep;3(5):439-47
references.pmid: 14961336
references.citation: J Clin Pharmacol. 1996 May;36(5):422-7
references.pmid: 8739021
references.citation: J Biosci Bioeng. 2002;93(2):176-82
references.pmid: 16233184
references.citation: Mar Biotechnol (NY). 1999 Nov;1(6):580-587
references.pmid: 10612683
references.citation: Antimicrob Agents Chemother. 2007 Jan;51(1):275-84
references.pmid: 17043127
references.citation: Can J Biochem Physiol. 1959 Aug;37(8):911-7
references.pmid: 13671378
references.citation: Biochim Biophys Acta. 1995 Apr 28;1256(1):52-6
references.pmid: 7742356
references.citation: J Agric Food Chem. 2002 Sep 11;50(19):5343-8
references.pmid: 12207472
references.citation: Carcinogenesis. 2000 Nov;21(11):2085-90
references.pmid: 11062172
references.citation: Arch Biochem Biophys. 2000 Jan 15;373(2):307-17
references.pmid: 10620354
references.citation: J Eukaryot Microbiol. 1999 Nov-Dec;46(6):637-47
references.pmid: 10568038
references.citation: Biochem Soc Trans. 1990 Feb;18(1):45-6
references.pmid: 2185084
references.citation: Br J Dermatol. 1992 Feb;126 Suppl 39:2-7
references.pmid: 1543672