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Appl Environ Microbiol, July 1998, p. 2676-2680, Vol. 64, No. 7
0099-2240/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Increased Carotenoid Production by the Food Yeast
Candida utilis through Metabolic Engineering of the
Isoprenoid Pathway
Hiroshi
Shimada,*
Keiji
Kondo,
Paul D.
Fraser,
Yutaka
Miura,
Toshiko
Saito, and
Norihiko
Misawa
Central Laboratories for Key Technology,
Kirin Brewery Co., Ltd., Kanazawa-ku, Yokohama-shi, Kanagawa 236, Japan
Received 15 December 1997/Accepted 16 April 1998
The yeast Candida utilis does not possess an endogenous
biochemical pathway for the synthesis of carotenoids. The central isoprenoid pathway concerned with the synthesis of prenyl lipids is
present in C. utilis and active in the biosynthesis of
ergosterol. In our previous study, we showed that the introduction of
exogenous carotenoid genes, crtE, crtB, and
crtI, responsible for the formation of lycopene from the
precursor farnesyl pyrophosphate, results in the C. utilis
strain that yields lycopene at 1.1 mg per g (dry weight) of cells (Y. Miura, K. Kondo, T. Saito, H. Shimada, P. D. Fraser, and N. Misawa, Appl. Environ. Microbiol. 64:1226-1229, 1998). Through
metabolic engineering of the isoprenoid pathway, a sevenfold increase
in the yield of lycopene has been achieved. The influential steps in
the pathway that were manipulated were 3-hydroxy methylglutaryl
coenzyme A (HMG-CoA) reductase, encoded by the HMG gene,
and squalene synthase, encoded by the ERG9 gene. Strains
overexpressing the C. utilis HMG-CoA reductase yielded lycopene at 2.1 mg/g (dry weight) of cells. Expression of the HMG-CoA
catalytic domain alone gave 4.3 mg/g (dry weight) of cells; disruption
of the ERG9 gene had no significant effect, but a
combination of ERG9 gene disruption and the overexpression
of the HMG catalytic domain yielded lycopene at 7.8 mg/g (dry weight)
of cells. The findings of this study illustrate how modifications in
related biochemical pathways can be utilized to enhance the production of commercially desirable compounds such as carotenoids.
*
Corresponding author. Present address: Department of
Biological Sciences, Faculty of Bioscience and Biotechnology, Tokyo
Institute of Technology, Nagatsuta, Midoriku, Yokohama 226, Japan.
Phone: 81-45-924-5737. Fax: 81-45-924-5805. E-mail:
hshimada{at}bio.titech.ac.jp.

Present address: Biochemistry Department, Royal Holloway University
of London, Egham, Surrey TW20 OEX, United Kingdom.
Appl Environ Microbiol, July 1998, p. 2676-2680, Vol. 64, No. 7
0099-2240/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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