A pathway for complete mineralization of the ambergris constituent (-)-Ambrox in Sphingomonas sp.

Authors

Tina Haupt, Felix Flachsmann, Gerhard Brunner, Yumiko Weiner-Sekiya, Lucas Hortencio, Cyrille Jarin, Patrick Robe, Alessio Fonzo, Francis Voirol, Eric Eichhorn, Andreas Natsch

Published in

Applied and environmental microbiology. Pages e0087626. Aug 05, 2026. Epub Aug 05, 2026.

Abstract

(-)-Ambrox, the smelling principle in ambergris of sperm whales, is a saturated polycyclic terpenoid ether with multiple tertiary and quaternary centers. Despite these structural features, it is readily biodegradable and thus represents an interesting case to understand the degradation pathway of a complex, saturated polycyclic terpene. We isolated two Sphingomonas spp. strains from activated sewage sludge capable of rapidly mineralizing (-)-Ambrox. The structures of seven isolated metabolites were determined by 2D-NMR, and further metabolite structures were proposed based on their exact masses. The use of two ¹³C-labeled substrates allowed completing the hypothesis for the biodegradation pathway. Biodegradation starts by oxidation of the α-C(4)-methyl group, followed by hydroxylation of the adjacent C(5)-angular CH-group, which allows opening of ring A by a unique retro-aldol process. β-Oxidation leads to a C11 metabolite, which is further degraded to a C6 δ-lactone. This metabolic fate is conserved among strains. The structure-biodegradation relationship indicates that only natural (-)-Ambrox and related labdanoids were mineralized, but not enantiomers and epimers. For both strains, the complete genome was sequenced; for one strain, a fosmid library was prepared, and the gene for the first oxidation step was cloned. The activity for the following step was located on a fosmid in a non-adjacent genomic region, indicating that this pathway is dispersed over the genome. This detailed study provides unique insights into the complex biodegradation pathway of the poorly studied class of saturated polycyclic terpenoids.
For complex, polycyclic natural substrates such as sesquiterpenes and diterpenes, there is little knowledge on biodegradation pathways, except for the elucidated steroid degradation pathways. This study presents key steps in the biodegradation pathway for (-)-Ambrox, a natural constituent of the sperm whale secretion ambergris, which was found to be readily biodegradable, despite a polycyclic ring system with multiple tertiary and quaternary carbon centers. This may be one of the first detailed studies on the biodegradation pathway of a polycyclic natural sesquiterpenoid.

PMID:
42554492
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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