Abstract
Squalene synthase inhibitors significantly accelerate the production of farnesol by various microorganisms. However, farnesol production by Saccharomyces cerevisiae ATCC 64031, in which the squalene synthase gene is deleted, was not affected by the inhibitors, indicating that farnesol accumulation is enhanced in the absence of squalene synthase activity. The combination of diphenylamine as an inhibitor of carotenoid biosynthesis and a squalene synthase inhibitor increases geranylgeraniol production by a yeast, Rhodotorula rubra NBRC 0870. An ent-kauren synthase inhibitor also enhances the production of farnesol and geranylgeraniol by a filamentous fungus, Gibberella fujikuroi NBRC 30336. These results indicate that the inhibition of downstream enzymes from prenyl diphosphate synthase leads to the production of farnesol and geranylgeraniol.
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Bansal VS, Vaidya S (1994) Characterization of two distinct allyl pyrophosphatase activities from rat liver microsomes. Arch Biochem Biophys 315:393–399
Bergstrom JD, Kurtz MM, Rew DJ, Amend AM, Karkas JD, Bostedor RG, Bansal VS, Dufresne C, Van Middlesworth FL, Hensens OD (1993) Zaragozic acids: a family of fungal metabolites that are picomolar competitive inhibitors of squalene synthase. Proc Natl Acad Sci USA 90:80–84
Bostedor RG, Karkas JD, Arison BH, Bansal VS, Vaidya S, Germershausen JI, Kurtz MM, Bergstrom JD (1997) FOH-derived dicarboxylic acids in the urine of animals treated with zaragozic acid A or with FOH. J Biol Chem 272:9197–9203
Chambon C, Ladeveze V, Oulmouden M, Servouse M, Karst F (1990) Isolation and properties of yeast mutants affected in farnesyl diphosphate synthase. Curr Genet 18:41–46
Fujii H, Koyama T, Ogura K (1982) Efficient enzymatic hydrolysis of polyprenyl pyrophosphates. Biochim Biophys Acta 712:716–718
Gerhard S (1997) High level expression of carotenogenic genes for enzyme purification and biochemical characterization. Pure Appl Chem 69:2163–2168
Hasumi K, Tachikawa K, Sakai K, Murakawa S, Yoshikawa N, Kumazawa S, Endo A (1993) Competitive inhibition of squalene synthase by squalestatin 1. J Antibiot 46:689–691
Jacob MH, Bessie WK, Kenneth WN (2003) FOH biosynthesis in Candida albicans: cellular response to sterol inhibition by zaragozic acid B. Antimicrob Agents Chemother 47:2366–2369
Machida K, Tanaka T, Yano Y, Otani S, Taniguchi M (1999) FOH-induced growth inhibition in Saccharomyces cerevisiae by a cell cycle mechanism. Microbiology 145:293–299
Meigs TE, Roseman DS, Simoni RD (1996) Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase degradation by the nonsterol mevalonate metabolite FOH in vivo. J Biol Chem 271:7916–7922
Nah J, Song SJ, Back K (2001) Partial characterization of farnesyl and geranylgeranyl diphosphatases induced in rice seedlings by UV-C irradiation. Plant Cell Physiol 42:864–867
Ohnuma S, Watanabe M, Nishino T (1996) Identification and characterization of GGOH kinase and geranylgeranyl phosphate kinase from the Archaebacterium Sulfolobus acidocaldarius. J Biochem 119:541–547
Po-Huang L, Tzu-Ping K, Andrew H-JW (2002) Structure, mechanism and function of prenyltransferases. Eur J Biochem 269:3339–3354
Rademacher W (2000) Effects on gibberellin biosynthesis and other metabolic pathways. Annu Rev Plant Physiol Plant Mol Biol 51:501–531
Radetich B, Corey EJ (2002) A general stereocontrolled, convergent synthesis of oligoprenols that parallels the biosynthetic pathway. J Am Chem Soc 124:2430–2431
Wang G, Tang W, Bidigare RR (2005) Terpenoids as therapeutic drugs and pharmaceutical agents. In: Zhang L, Demain AL (eds) Natural products. Humana, NJ, pp 197–227
Acknowledgment
We thank Prof. T. Sassa (Faculty of Agriculture, Yamagata University) for the technical advice regarding cultivation of G. fujikuroi and gibberellin inhibitors.
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Muramatsu, M., Ohto, C., Obata, S. et al. Accumulation of prenyl alcohols by terpenoid biosynthesis inhibitors in various microorganisms. Appl Microbiol Biotechnol 80, 589–595 (2008). https://doi.org/10.1007/s00253-008-1578-z
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DOI: https://doi.org/10.1007/s00253-008-1578-z