2 完全重水素化メバロン酸を用いるイソプレノイド類の代謝反応機構化学への応用(口頭発表の部)

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Isoprenoids are chemically diverse in nature, ubiquitous in living organisms, and crucial in biological processes. The biosynthesis of such isoprenoids proceeds through mevalonate and nonmevalonate pathways depending upon organisms and cellular organella, isopentenyl diphosphate (IPP) being a key intermediate in both cases. Metabolic engineering and control of these pathways should thus provide new opportunity to study intriguing chemistry and biochemistry involved and to develop selective chemotherapeutic agents and isoprenoid-related materials. We describe a new practical approach to the preparation of highly- and multiply deuterated isoprenoids, zeaxanthin and diterpene anitibiotic terpentecin being as examples, and its potential for analyzing the biosynthetic mechanism of isoprenoids, based on the metabolic engineering of microorganisms. Obviously, deuterium-labeled compounds are invaluable in biochemical, bioorganic as well as physicochemical research. Metabolically engineered E. coli DK223 (pTMV20, pACCAR25ΔcrtX) produces zeaxanthin under the presence of mevalonate. Fully deuterated mevalonolactone-d_9 (MVL-d_9), which had been synthesized, was supplemented to the culture of the above triply-engineered E. coli, and the biosynthesized zeaxanthin was extracted and purified by repeated chromatography. All the zeaxanthin formed was proved to be derived only from the supplemented MVL-d_9. This was the first example of such highly and multiply deuterated zeaxanthin, and clearly demonstrated significant potential of the present approach for the preparation of various isotope-labeled isoprenoids. Additional example of this approach was also demonstrated in the mechanistic study of cyclization reaction in the biosynthesis of diterpene anitibiotic terpentecin. Straightforward stereochemical analysis of isoprenoid biosynthesis was demonstrated by one-shot labeling of MVL-d_9 and ^1H NMR spectroscopy. Precise analysis of the simplified proton spectra of highly deuterated isoprenoids, especially under the deuterium decoupled conditions, appeared to be beneficial for mechanistic enzymology, particularly, for the key transformation involving proton attack and proton quench as observed in the terpene cyclase reactions.
天然有機化合物討論会の論文
2001-09-01

2 完全重水素化メバロン酸を用いるイソプレノイド類の代謝反応機構化学への応用(口頭発表の部)

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