Directing Biosynthesis VI - Book of abstracts

Exploring the chemical diversity of bartolosides – a group of cyanobacterial chlorinated dialkylresorcinols João Reis 1 , Pedro Nuno LEÃO 2 1 ICBAS, University of Porto, Portugal, 2 (CIIMAR), University of Porto, Portugal Cyanobacteria are rich in biosynthetic gene clusters that encode the production of a variety of chemically diverse metabolites. Such small molecules can serve as starting points for drug discovery and the enzymes that participate in their biosynthesis may give rise to useful biocatalysts. We have recently showed that the bartolosides, a group of diverse cyanobacterial dialkylresorcinols, are esterified in their chlorinated alkyl positions with free fatty acid carboxylates, by the C-O bond-generating BrtB, encoded in the brt cluster. [1-3] This enzyme belongs to a poorly explored family from which only one other member is characterized – CylK, involved in the biosynthesis of the cylindrocyclophanes. Previously reported bartolosides feature one or two glycosyl moieties and different levels of halogenation. With the discovery of BrtB we revealed an additional series of novel fatty acid branched bartolosides. [3] Here, we show our most recent screening for bartoloside producing strains in the LEGE-CC, a culture collection with over 400 cyanobacterial strains. We coupled PCR screening and the Global Natural Products Social Molecular Networking (GNPS)-based metabolomics to detect additional brt clusters in the LEGE-CC strains and new bartoloside derivatives, respectively. Additionally, we show our in silico analysis of BrtB enzymes using the Enzyme Function Initiative Tools and their diversity in the LEGE-CC. With these approaches, we catalog bartoloside chemical diversity and study the diversity of BrtB homologs. References 1. Leao, P. N.; Nakamura, H.; Costa, M.; Pereira, A. R.; Martins, R.; Vasconcelos, V.; Gerwick, W. H.; Balskus, E. P., Biosynthesis-assisted structural elucidation of the bartolosides, chlorinated aromatic glycolipids from cyanobacteria. Angew Chem Int Ed Engl 2015, 54 (38), 11063-7 2. Afonso, T. B.; Costa, M. S.; Rezende de Castro, R.; Freitas, S.; Silva, A.; Schneider, M. P.; Martins, R.; Leao, P. N., Bartolosides E-K from a Marine Coccoid Cyanobacterium. J Nat Prod 2016, 79 (10), 2504-2513 3. Reis, J. P. A.; Figueiredo, S. A. C.; Sousa, M. L.; Leão, P. N., BrtB is an O-alkylating enzyme that generates fatty acid- bartoloside esters. Nat Commun 2020, 11 (1), 1458

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