Planta Med 2015; 81 - IL13
DOI: 10.1055/s-0035-1556110

Discovery of novel chlorinated acyl amides from a marine cyanobacterium using integrated technologies

K Kleigrewe 1, J Almaliti 1, I Yuheng Tian 1, 2, RB Kinnel 3, A Korobeynikov 4, 5, 6, EA Monroe 1, 7, BM Duggan 10, V Di Marzo 8, DH Sherman 9, PC Dorrestein 10, L Gerwick 1, WH Gerwick 1, 10
  • 1Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, USA
  • 2University of California Berkeley, USA
  • 3Hamilton College, Clinton, NY, USA
  • 4Faculty of Mathematics and Mechanics, Saint Petersburg State University, Russia
  • 5Center for Algorithmic Biotechnology, Saint Petersburg State University, Russia
  • 6Algorithmic Biology Laboratory, Saint Petersburg Academic University, Russia
  • 7Department of Biology, William Paterson University of New Jersey, USA
  • 8Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Italy
  • 9Life Sciences Institute, University of Michigan, Ann Arbor, Michigan
  • 10Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, USA

An innovative approach was developed for the discovery of new natural products by combining mass spectrometric metabolic profiling with genomic analysis, and resulted in the discovery of the columbamides, a new class of di- and tri-chlorinated acyl amides with cannabinomimetic activity. By genome analysis, a presumed regulatory domain was identified upstream of several previously described biosynthetic gene clusters in two cyanobacteria, and a similar regulatory domain was identified in the M. bouillonii PNG genome. A corresponding downstream biosynthetic gene cluster was located and carefully analyzed. Subsequently, MS-based molecular networking identified a series of candidate products, and these were isolated and their structures rigorously established.