TY - JOUR

T1 - Combining Mass Spectrometric Metabolic Profiling with Genomic Analysis: A Powerful Approach for Discovering Natural Products from Cyanobacteria

AU - Kleigrewe, K.

AU - Almaliti, J.

AU - Tian, I.Y.

AU - Kinnel, R.B.

AU - Korobeynikov, A.

AU - Monroe, E.A.

AU - Duggan, B.M.

AU - Di Marzo, V.

AU - Sherman, D.H.

AU - Dorrestein, P.C.

AU - Gerwick, L.

AU - Gerwick, W.H.

PY - 2015

Y1 - 2015

N2 - © 2015 The American Chemical Society and American Society of Pharmacognosy. 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 trichlorinated acyl amides with cannabinomimetic activity. Three species of cultured marine cyanobacteria, Moorea producens 3L, Moorea producens JHB, and Moorea bouillonii PNG, were subjected to genome sequencing and analysis for their recognizable biosynthetic pathways, and this information was then compared with their respective metabolomes as detected by MS profiling. By genome analysis, a presumed regulatory domain was identified upstream of several previously described biosynthetic gene clusters in two of these cyanobacteria, M. producens 3L and M. producens JHB. A similar regulatory domain was identified in the M. bouillonii PNG genome, and a corresponding downstream biosynthetic gene cluster was located a

AB - © 2015 The American Chemical Society and American Society of Pharmacognosy. 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 trichlorinated acyl amides with cannabinomimetic activity. Three species of cultured marine cyanobacteria, Moorea producens 3L, Moorea producens JHB, and Moorea bouillonii PNG, were subjected to genome sequencing and analysis for their recognizable biosynthetic pathways, and this information was then compared with their respective metabolomes as detected by MS profiling. By genome analysis, a presumed regulatory domain was identified upstream of several previously described biosynthetic gene clusters in two of these cyanobacteria, M. producens 3L and M. producens JHB. A similar regulatory domain was identified in the M. bouillonii PNG genome, and a corresponding downstream biosynthetic gene cluster was located a

U2 - 10.1021/acs.jnatprod.5b00301

DO - 10.1021/acs.jnatprod.5b00301

M3 - Article

VL - 78

SP - 1671

EP - 1682

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 7

ER -