Structural requirements for transformation of substrates by the (S)-adenosyl-L-methionine:delta 24(25)-sterol methyl transferase

The biosynthesis of steroids and triterpenoids

“…1137 SMT from sunflower uses cycloartenol preferentially over other substrates including zymosterol (78) (in contrast to the yeast enzyme which is specific for zymosterol -see preceding section): only a nucleophilic centre at C-3 and the 24 -double bond appear to be obligatory structural features for substrate binding and methylation; in addition, the cycloartenol nucleus is suggested to assume a flat (rather than a bent) conformation in the enzyme-substrate complex. 1136 Nes has proposed that the methyl group adds to C-24 of the double bond from the si-face in Zea mays, 1138 as found for fungi and marine organisms (although previous investigators have identified addition to the re-face for this species), and this is supported by results from Ajuga reptans. 1139 Subsequent hydride migration of H-24 to C-25, converting the C-25 cation to a C-24 cation, would then be expected to occur via what was the re-face of the double bond 1140,1141 and Seo has obtained experimental evidence for re-face hydrogen migration in Physalis peruvina.…”

“…Biosynthesis of sitosterol from cycloartenol commences with transfer of a methyl group from (S)-adenosyl--methionine (AdoMet; SAM) to C-24 of cycloartenol, catalysed by the enzyme (S)-adenosyl--methionine: 24(25) -sterol methyl transferase (SMT) to yield 24(28) -methylene cycloartanol (82), which has been suggested to be the rate-limiting step in phytosterol biosynthesis. 123,1136 An alternative methylation reaction yielding a 23(24) -steroid (86) has been shown to require a different SMT. 1137 SMT from sunflower uses cycloartenol preferentially over other substrates including zymosterol (78) (in contrast to the yeast enzyme which is specific for zymosterol -see preceding section): only a nucleophilic centre at C-3 and the 24 -double bond appear to be obligatory structural features for substrate binding and methylation; in addition, the cycloartenol nucleus is suggested to assume a flat (rather than a bent) conformation in the enzyme-substrate complex.…”

Structural requirements for substrate recognition of Mycobacterium tuberculosis 14α-demethylase: implications for sterol biosynthesis

“…It was reported that maize 14␣-demethylase is unable to metabolize cycloeucalenol, the 24-methyl isomer of 31-norcycloartenol (5). Cycloartenol, however, is the best substrate for sunflower sterol methyl transferase (SMT), another enzyme involved in sterol biosynthesis in plants and fungi (34). Knowing that the 9␤,19-cyclopropyl sterols are obtusifoliol precursors in higher plants (20,21), the SMT activity should occur before the 14␣-demethylation in the plant sterol biosynthesis sequence.…”

“…Knowing that the 9␤,19-cyclopropyl sterols are obtusifoliol precursors in higher plants (20,21), the SMT activity should occur before the 14␣-demethylation in the plant sterol biosynthesis sequence. The plant 14␣-demethylase preference for 31-nor-sterols suggests that the 4␤-demethylation might occur before 14␣-demethylation and SMT activity (34). Conversely, yeast S. cerevisiae SMT shows a preference for zymosterol, suggesting that this activity probably takes place after 14␣-demethylation and 4-demethylation in the ergosterol biosynthesis (18).…”

Sterol Metabolism

“…Because the chemical structures of 24-methylene cyclartanol and 24-methylene lophenol are very different, it has been suggested that the two methylation ractions would be catalyzed by two different enzymes (Rahier et al, 1986). However, since no plant SMT has been purified so far, the hypothesis of an unique plant SMT catalyzing both alkylations (Nes et al, 1991) should also be considered. The first SMT gene (ERG6) cloned was from S.cerevisiae (Gaber et al, 1989;Hardwick and Pelham, 1994).…”