Biosynthese de la chaine lateale ethyle du stigmastanol et du stigmasten-22,ol-3beta du myxomycete Dictyostelium discoideum

Abstract

(Repu le 7 mai/l2 octobre 1971) Several laboratories have shown that the two carbon atoms C-28 and C-29 of the ethyl or ethylidene side chains of phytosterols are introduced on to a C-24 unsaturated side chain by two methylation steps. A scheme based on previous work suggests the various intermediates which can be formed by stabilisation of the carbonium ion 3. We have shown previously that in the biosynthesis of 50i-stigmastan-3p-01 ( l l a ) and 5a-stigmast-22-en-3/3-01 (12a), sterols of the myxomycete Dictyosteliurn discoideurn, routes h and i could be excluded.I n the present paper we describe the in vivo conversion, by the myxomycete, of differently labelled lanosterol (13), stigmastanol ( l l c ) , and 5a-stigmast-22-en-3p-01 (12c), into the sterols 12a and l l a , and discuss the possible biosynthetic routes for the two sterols.After incorporation of a mixture of [26,27-14C2]lanosterol and [24-3H]lanosterol (3H/14C = 5.60 & 0.25), the isolated sterols l l a and 12a were converted into l l b (3H/14C = 5.54 0,28) and 14b (3H/14C = 5.61By ozonisation followed by oxidation in neutral or basic medium, 12a was converted into the esters 15 (3H/14C = 5.54 0.3), respectively. These results show that during the C-24 methylation, H-24 is not lost; the hydrogen which is lost is located neither a t C-24 nor a t C-23 and must therefore be a t C-25. This excludes routes a and b for sterol 12.After incorporation of a mixture of [26,27-14C2] These results show that during the conversion of 13 into 12a, 50°/, of the H-23 atoms migrate from C-23 to (2-24 and 25O/, remain on C-23 ; the other 25O/, are eliminated. During the conversion of 13 into l l a both H-23 atoms are retained. These results excluded route g for the two sterols. Since we have demonstrated that the conversion of l l c into 12a is possible in high yields (4.60/,) with an efficiency eight times greater than the conversion of 12c into l l a , we propose that the sterol l l a is synthesized in vivo according to route e with migration of H-23 from C-23 to C-24. The sterol 12a is biosynthetized either by route d, f, the 22,23 double bond being introduced during the alkylation step, or by desaturation of the sterol l l a , the C-22, C-23 double bond being introduced after the C-24 alkylation. 0.28).0.28) and 16 (3H/14C = 5.55 0.15).Les etudes de biosynthese des chaines ethyle et Bthylidbne en C-24 des phytosterols ont montre que les deux atomes de carbone proviennent de la mkthionine [1-3,3a].Plusieurs mecanismes ont kt6 proposes pour expliquer cette double methylation [I-81 (voir schirma) : la premiere methylation du prdcurseur sterolique 1 conduit B la formation d'un intermediaire methylenique 2, qui peut servir de substrat B une deuxiitme methylation pour donner le carbocation intermediaire 3. Le carbocation 3 peut, apres stabilisation, soit par elimination d'un proton, soit par fixation d'un ion hydrure, conduire B des composes portant deux atomes de carbone derivant du groupe methyle de la methionine. Si

Sterol phylogenesis and algal evolution.

“…2). ated compounds (data not shown) as shown by Lederer and :yclolaudenol in coworkers (27,28). The mechanism of C-24 alkylation pery mechanism b formed by D. discoideum is therefore mechanism a or the one or mechanism b following the A24 (28) …”

“…The GLC chromatogram of the ethereal extract of saponified cells indicated that several [not just two as previously thought (26)(27)(28)] compounds may be steroidal (Fig. 3).…”

“…Sterol characterization and biosynthesis in I and II has been the subject of several investigations (25)(26)(27)(28)(29). Ergosterol was the only sterol detected in I while two sterols-dictyosterol and 22-dihydrodictyosterol (24p-ethylcholestanol)-were detected in II (Fig.…”

“…The results demonstrate that the 24.3 configuration is formed by different alkylation routes in I and II. The A25 (27) route operates in I while the A24 (28) …”

Effect of cerulenin on the growth and differentiation of Dictyostelium discoideum

“…discoideum (12,15). In addition, approximately 5% of the sterol content had a retention time characteristic of stigasmanol, which has been shown to be a minor sterol constituent in D. discoideum (7). The remaining sterol component, 5 to 10o of the total, has yet to be identified.…”