title: Biochemometrics for Natural Products Research: Comparison of Data Analysis Approaches and Application to Identification of Bioactive Compounds.
abstract: A central challenge of natural products research is assigning bioactive compounds from complex mixtures. The gold standard approach to address this challenge, bioassay-guided fractionation, is often biased toward abundant, rather than bioactive, mixture components. This study evaluated the combination of bioassay-guided fractionation with untargeted metabolite profiling to improve active component identification early in the fractionation process. Key to this methodology was statistical modeling of the integrated biological and chemical data sets (biochemometric analysis). Three data analysis approaches for biochemometric analysis were compared, namely, partial least-squares loading vectors, S-plots, and the selectivity ratio. Extracts from the endophytic fungi Alternaria sp. and Pyrenochaeta sp. with antimicrobial activity against Staphylococcus aureus served as test cases. Biochemometric analysis incorporating the selectivity ratio performed best in identifying bioactive ions from these extracts early in the fractionation process, yielding altersetin (3, MIC 0.23 μg/mL) and macrosphelide A (4, MIC 75 μg/mL) as antibacterial constituents from Alternaria sp. and Pyrenochaeta sp., respectively. This study demonstrates the potential of biochemometrics coupled with bioassay-guided fractionation to identify bioactive mixture components. A benefit of this approach is the ability to integrate multiple stages of fractionation and bioassay data into a single analysis.
authors: Department of Chemistry & Biochemistry, University of North Carolina Greensboro , Greensboro, North Carolina 27402, United States.
authors: Joshua J
authors: JJ
authors: Kellogg
authors: Department of Chemistry & Biochemistry, University of North Carolina Greensboro , Greensboro, North Carolina 27402, United States.
authors: Daniel A
authors: DA
authors: Todd
authors: Department of Chemistry & Biochemistry, University of North Carolina Greensboro , Greensboro, North Carolina 27402, United States.
authors: Joseph M
authors: JM
authors: Egan
authors: Department of Chemistry & Biochemistry, University of North Carolina Greensboro , Greensboro, North Carolina 27402, United States.
authors: Huzefa A
authors: HA
authors: Raja
authors: Department of Chemistry & Biochemistry, University of North Carolina Greensboro , Greensboro, North Carolina 27402, United States.
authors: Nicholas H
authors: NH
authors: Oberlies
authors: Department of Chemistry, University of Bergen , Bergen 5020, Norway.
authors: Olav M
authors: OM
authors: Kvalheim
authors: Department of Chemistry & Biochemistry, University of North Carolina Greensboro , Greensboro, North Carolina 27402, United States.
authors: Nadja B
authors: NB
authors: Cech
mesh_terms: D000528:Alternaria / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology; D006571:Heterocyclic Compounds; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D006571:Heterocyclic Compounds; C097798:macrosphelide A