P89
Combining Mass Spectrometric Metabolic Profiling with Genomic Analysis: A Powerful Tool for Revealing New Natural Products in Cyanobacteria
Sunday, January 11, 2015
California Ballroom C and Santa Fe Room
Karin Kleigrewe, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, Isaac Yuheng Tian, University of California Berkeley, Robin B. Kinnel, Hamilton College, Clinton, NY, Anton Korobeynikov, Saint Petersburg State University, Pavel Pevzner, Department of Computer Science and Engineering, University of California San Diego, David H. Sherman, Life Sciences Institute & Associate Dean for Research and Graduate Education, University of Michigan, Ann Arbor, MI, Pieter C. Dorrestein, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, Lena Gerwick, Gerwick Laboratory, Scripps Institution of Oceanography, San Diego, CA and William Gerwick, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA
Cyanobacteria are exceptionally talented in synthesizing natural products that are structurally unique. However, genome sequencing has revealed that microbial life, including marine cyanobacteria, have much more capacity for natural product biosynthesis than was appreciated from isolation studies. To obtain insight into compound classes produced by cyanobacteria versus compounds that should be present based on their genomes, mass spectrometric (MS) metabolic profiles of
Moorea producens 3L,
Moorea producens JHB and
Moorea bouillonii PNG were compared to the biosynthetic pathways suggested from their sequenced genomes.
The “Global Natural Products Social Molecular Networking” (GNPS) tool was used to analyze MS-fragmentation patterns derived from Moorea natural product extracts. This provided a rapid overview of the compound classes present, and those shared between Moorea species. This chemical analysis was followed by a bioinformatics investigation of the three Moorea genomes for their potential to produce secondary metabolites. We searched for typical polyketide synthase (PKS) and nonribosomal peptide synthase (NRPS) genes using previously characterized cyanobacterial biosynthetic pathways like those for curacin, jamaicamide and hectochlorin. Through extensive comparisons between MS-networking and biosynthetic pathways, a specific genomic region was identified upstream of the pathways which appears to encode for the production of large amounts of natural products in M. producens 3L and M. producens JHB. The biosynthetic pathway next to this upstream genome region in M. bouillonii PNG was undescribed; nevertheless, MS-profiling indicated its likely presence in considerable abundance. Isolation and subsequent structure elucidation yielded a new class of acyl amides whose biosynthetic assembly matches the identified gene cluster.
