Sterol Biosynthesis in Sponges

Whereas our knowledge about the sterols present in sponges has rapidly increased in the last few years, our insight into the metabolism of sterols in these animals is still very meagre. 

By working with a very small amounts of material Walton and Pennock 182) observed that the sponge Grantia compressa utilized C-mevalonate for the biosynthesis of isoprenoids (squalene, steroids and ubiquinones) in direct contrast with the complete absence of radioactivity in the terpenoids of Suberites domuncula incubated with C-mevalonate. 

Clearly, much work is required before any definite conclusions can be drawn about sterol metabolism in sponges. The exogenous sterol requirement is a characteristic of many lower organisms, the majority being invertebrates. Within the invertebrates, the position is still rather confusing as to which members can or cannot synthesize sterols. Literature reports are often conflicting, not only within the phylum, class and order, but even within the species. 

A very useful survey of current knowledge of sterol biosynthesis in invertebrates has recently been authored by Rees and Goodwin (755). 

The literature which reports the occurrence of amines and, more generally, products associated with aminoacid metabolism in marine invertebrates results largely from work of Ackermann which extended over a number of years (2). A brief summary of nitrogen compounds in Porifera by L. S. CiERESZKO 43) appeared in 1970. 

---

Silva, C.J., Wiinsche, L., and Djerassi, C. (1991) Biosynthetic studies of marine lipids 35. The demonstration of de novo sterol biosynthesis in sponges using radiolabelled isoprenoid precursors. Comp. Biochem. Physiol, 99B, 763-773. 

Steroid chemistry, the glamor area of natural product research in the years following World War II, was replaced by macrolides, alkaloids, and prostanoids. Sterol chemistry again became exciting when an unanticipated rich diversity of marine invertebrate sterols were isolated, notably from sponges. After pioneering research in Italy, the field was reborn in Carl Djerassi s laboratory at Stanford. As a result, we now have a better and more detailed knowledge of sterol biosynthesis than of any other class of marine natural products. The authors of Chapter 1 are Stanford alumni. 

A recent and surprising finding in sponge sterol biosynthesis is the observation that certain 24-alkyl sterols can be transformed to cholesterol [46,48, 50]. This is particularly unusual, as this pathway operates in organisms which are also... 

Sodano, G. (1979) Non-conventional sterols from marine sponges occurrence and biosynthesis, in Biologic des Spongiaires (eds C. Lwi and N. Boury-Esnault), Colloques Internationaux du CNRS, No. 291, Editions du CNRS, Paris, pp. 393-399. 

One of the first biosynthetic investigations undertaken in the Djerassi laboratory dealt with the sponge Aplysina fistularis. This sponge contains sterols with side-chain alkylations at C-24 and C-26, the aplysterols [37], The biosynthesis of these unconventional sterols was shown (Scheme 7) to proceed by a conversion of desmosterol (34) to epicodisterol (51) [but not its C-24 epimer, codisterol (52)] followed by methylation to 25(27)-dehydroaplysterol (53). Sterol... 

The biosynthesis of pregnenelone (112) in mammals has been well documented [1] it is known to be produced from cholesterol (1) via its 20,22-dihydroxy derivative (121) (Scheme 19A). The origin of 112 has been investigated in the sponge Amphimedon compressa. At the present time it is not known whether cholesterol and its 20,22-dihydroxy derivative serve as precursors for this pregnane in A. compressa however a new pathway (Scheme 19B) has been found to operate [89]. This involves the conversion of 22-dehydro sterols (e.g. stigmasterol, 122) to pregnenelone. The mechanism is believed to... 

De Rosa, M., Minale, L., and Sodano, G., Metabolism in porifera. I. Some studies on the biosynthesis of fatty acids, sterols and bromo compounds by the sponge Verongia aerophoba, Comp. Biochem. Physiol., 45B, 883, 1973. 

Other biogenetically distinct cyclopropane side chain substitution patterns are typified by the sponge sterols calysterol (25) isolated from Calyx nicaensis, and petrosterol (19) found in Petrosia. Unlike the biosynthesis of gorgosterol-type (17)... 

Stoilov, I.L., J.E. Thompson, J-H. Cho, and C. Djerassi Biosynthetic studies of marine lipids. Stereochemical aspects and hydrogen migrations in the biosynthesis of the triply alkylated side chain of the sponge sterol strongylosterol. J. Am. Chem. Soc. 108, 8235 (1986). 

Kerr, R.G., Kerr, S.L, and Djerassi, C. (1991b) Biosynthetic studies of marine lipids. 26. Elucidation of the biosynthesis of mutasterol, a sponge sterol with a quaternary carbon in its side chain. J. Org. Chem., 56,63-66. 

Margot, C., Catalan, C.A.N., Proudfoot, J.R., Sodano, G., Sica, D and Djerassi, C. (1987) Biosynthesis of three cydopropen-containing sterols in the sponge Calyx niceaensis. J. Chem. Soc. Chem. Commun., 1441-1442. 

Silva, C.J. and Djerassi, C. (1991) Sterols in marine invertebrates. Part 64. Isolation, stereochemistry, and biosynthesis of sormosterol, a novel cyclopropane-containing sponge sterol. Collect. Czech. Chem. Commun., 56, 1093-1105. 

Stoilov, I.L., Back, T.G., Thompson, J.E., and Djerassi, C. (1986b) Biosynthetic studies of marine lipids. 8. Comse of the stereoselective alkylation and regioselective hydrogen migration in the biosynthesis of the sponge sterol 24(S)-24-isopropenylcholesterol. Tetrahedron, 42, 4156 160. 

---