CIIMAR’s Neptune Seminar with Anne Liong | Boca da Baleia
Halogenation is an important strategy in the biosynthesis of natural products and medicinal chemistry for modifying the properties of molecules. Here, we present the discovery of trichlorinated secondary metabolites, the lebomboamides, which are produced by the cyanobacterium Nostoc sp. LEGE 12454. Structural analysis revealed a γ-chloro, δ-gem-dichloro acyl unit. We identified a biosynthetic gene cluster encoding a single non-heme Fe(II)/α-ketoglutarate-dependent halogenase, LbbB. In vitro experiments demonstrated that LbbB catalyses the triple chlorination of fatty acyl substrates – the first instance of a halogenase performing three halogenations on sp³ carbons. The enzyme also exhibits flexibility in halogenation and oxygenation products and can accept bromine. We observed similar behaviour in related halogenases, suggesting that this enzyme family can be fine-tuned to obtain different halogenated fatty acyl moieties.
Anne Liong completed her MSc in Molecular and Applied Biotechnology at RWTH Aachen University and joined CNP in 2020. She is currently a PhD student in Biomedical Sciences at ICBAS, University of Porto. Her research focuses on cyanobacterial natural products and the exploration of new biosynthetic pathways, combining mass spectrometry-guided discovery, enzymology, protein-function prediction, and characterization of unknown biosynthetic gene clusters. She is particularly interested in fatty acid-activating enzymes (FAALs) and halogenases in cyanobacterial secondary metabolism.
In case of any questions, please contact CIIMAR’s Seminar team, Marta Monteiro, Miguel Semedo, & Paulo Oliveira, at seminars@ciimar.up.pt
CIIMAR members can also access last seminars recordings through the LINK.