Formation of Developmentally Toxic Phenanthrene Metabolite Mixtures by Mycobacterium sp. ELW1

Abstract

Mycobacterium sp. ELW1 co-metabolically degraded up to 1.8 µmol phenanthrene (PHE) in ~48 hours (hr) and the formation of hydroxyphenanthrene (OHPHE) metabolites, including 1-hydroxyphenanthrene (1-OHPHE), 3-hydroxyphenanthrene (3-OHPHE), 4-hydroxyphenanthrene (4-OHPHE), 9-hydroxyphenanthrene (9-OHPHE), 9,10-dihydroxyphenanthrene (1,9-OHPHE), and trans-9,10-dihydroxy-9,10-dihydrophenanthrene (trans-9,10-OHPHE), were identified and quantified over time. The monooxygenase responsible for co-metabolic transformation of PHE was inhibited by 1-octyne. First-order PHE transformation rates, kPHE, and half-lives, t1/2, for PHE-exposed cells ranged 0.16 – 0.51 hr−1 and 1.4 – 4.3 hr, respectively, and the 1-octyne controls ranged 0.015 – 0.10 hr−1 and 7.0 – 47 hr, respectively. While single compound standards of PHE and trans-9,10-OHPHE, the major OHPHE metabolite formed by ELW1, were not toxic to embryonic zebrafish (Danio rerio), single compound standards of minor OHPHE metabolites, 1-OHPHE, 3-OHPHE, 4-OHPHE, 9-OHPHE, and 1,9-OHPHE, were toxic, with effective concentrations (EC50s) ranging from 0.5– 5.5 µM. The metabolite mixtures formed by ELW1, and the reconstructed standard mixtures of the identified OHPHE metabolites, elicited a toxic response in zebrafish for the same 3 time points. EC50s for the metabolite mixtures formed by ELW1 were lower (more toxic) than those for the reconstructed standard mixtures of the identified OHPHE metabolites. Ten unidentified hydroxy PHE metabolites were measured in the derivatized mixtures formed by ELW1 and may explain the increased toxicity of the ELW1 metabolites mixture, relative to the reconstructed standard mixtures of the identified OHPHE metabolites.

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Untangling mechanisms of crude oil toxicity: linking gene expression, morphology and PAHs at two developmental stages in a cold-water fish

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