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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,dagger 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.

dagger 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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