Biosynthesis of ambrein in ambergris: evidence from isotopic data and identification of possible intermediates

Abstract

Ambrein is found in ambergris, a coprolith occurring in the rectum of the sperm whale. In vitro, ambrein is produced by enzymatic cyclisation of squalene, via a monocyclic intermediate. However, little is known of the in vivo process. In order to find evidence for the reaction in vivo, a comparison was made of the δ¹³C relative isotopic ratios of ambrein in ambergris with those of co-occurring sterols. A statistically significant difference was noted. This suggests that ambrein originates via a different biosynthetic mechanism from that of the sterols. Examination of the minor constituents of a hydrogenolysed extract of ambergris revealed compounds with a bicyclic polypodane nucleus, rather than those with monocyclic structures. It is hypothesised that in vivo biosynthesis of ambrein proceeds, at least in some cases, via bacterial production of bicyclic polypodenols. The latter are known products of non-concerted squalene (or squalene oxide) cyclisations in other organisms.

Graphical Abstract

Keywords:

• Ambergris
• polypodane
• ambrein
• sperm whale
• Physeter macrocephalus

Acknowledgements

We are grateful to A. Wells and J. Smith (Ambergris Connect Ltd) for pieces of an ambergris sample found by Tomás Helle Pessot, Salvador Mansilla Bastías and Nathan Wolff Reinarz of Universidad Austral de Chile (details reported by Rowland et al. 2018c). We thank D. Payne (formerly University of Plymouth) for column chromatography fractions of an extract of the latter ambergris sample, isolated as reported previously (Rowland et al. 2018c).

Disclosure statement

No potential conflict of interest was reported by the authors.