The stereochemistry of hexahydroprenol, ubiquinone and ergosterol biosynthesis in the mycelium of Aspergillus fumigatus Fresenius

Abstract

1. The mycelium of Aspergillus fumigatus has been shown to incorporate mevalonate into squalene, ubiquinone, ergosterol and hexahydroprenol. 2. The (3)H/(14)C ratio in ubiquinone, biosynthesized from [2-(14)C-(4R)-4-(3)H(1)]mevalonate, is the same as in the squalene; essentially no (3)H was incorporated from [2-(14)C-(4S)-4-(3)H(1)]mevalonate, indicating the biosynthesis of biogenetically trans-isoprene units. 3. The (3)H/(14)C ratio for ergosterol (from ;4R-mevalonate') was 3:5, showing that the proton at C-24 is not lost during alkylation of the side chain; it probably migrates to C-25. 4. As (3)H from both mevalonates was incorporated into the hexahydroprenols the biosynthesis of both cis- and trans-isoprene units must occur. 5. The saturated omega- and psi-isoprene units are shown to be biogenetically trans, as are two of the unsaturated residues. 6. The saturated alpha- and unsaturated beta-isoprene residues are both biogenetically cis. 7. An inexplicable loss of approximately half of the olefinic protons from the cis-portion of hexahydroprenol occurs; possible reasons for this loss are discussed. 8. Increase in chain length of the hexahydroprenols is by a cis addition. 9. A biosynthesis of hexahydroprenols by addition of cis-isoprene units to all-trans-geranylgeranyl pyrophosphate, or a dihydro or tetrahydro derivative thereof, is suggested.