D-Peptidase Activity in a Marine Mollusk Detoxifies a Nonribosomal Cyclic Lipopeptide: An Ecological Model to Study Antibiotic Resistance

Laurine Darcel (1) , Louis Bornancin (1) , Delphine Raviglione (1) , Isabelle Bonnard (1) , Suzanne Mills (1) , Julio Sáez-Vásquez (2) , Bernard Banaigs (1) , Nicolas Inguimbert (1)

1 CRIOBE - Centre de recherches insulaires et observatoire de l'environnement
2 LGDP - Laboratoire Génome et développement des plantes

In the marine environment, sessile cyanobacteria have developed chemical strategies for protection against grazers. In turn, herbivores have to circumvent these defenses and in certain cases even take advantage of them as shelter from their own predators. This is the case of Stylocheilus striatus, a sea hare that feeds on Anabaena torulosa, a cyanobacterium that produces toxic cyclic lipopeptides of the laxaphycin B family. S. striatus consumes the cyanobacterium without being affected by the toxicity of its compounds and also uses it as an invisibility cloak against predators. In this article, using different substrates analogous to laxaphycin B, we demonstrate the presence of an enzyme in the digestive gland of the mollusk that is able to biotransform laxaphycin B derivatives. The enzyme belongs to the poorly known family of d-peptidases that are suspected to be involved in antibiotic resistance.

Domains: Medicinal Chemistry

Laurine Darcel, Louis Bornancin, Delphine Raviglione, Isabelle Bonnard, Suzanne Mills, et al.. D-Peptidase Activity in a Marine Mollusk Detoxifies a Nonribosomal Cyclic Lipopeptide: An Ecological Model to Study Antibiotic Resistance. Journal of Medicinal Chemistry, In press, ⟨10.1021/acs.jmedchem.1c00249⟩. ⟨hal-03212973⟩