TY - JOUR
T1 - Advanced identification of global bioactivity hotspots via screening of the metabolic fingerprint of entire ecosystems
AU - Mueller, Constanze
AU - Kremb, Stephan
AU - Gonsior, Michael
AU - Brack-Werner, Ruth
AU - Voolstra, Christian R.
AU - Schmitt-Kopplin, Philippe
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Natural products (NP) are a valuable drug resource. However, NP-inspired drug leads are declining, among other reasons due to high re-discovery rates. We developed a conceptual framework using the metabolic fingerprint of entire ecosystems (MeE) to facilitate the discovery of global bioactivity hotspots. We assessed the MeE of 305 sites of diverse aquatic ecosystems, worldwide. All samples were tested for antiviral effects against the human immunodeficiency virus (HIV), followed by a comprehensive screening for cell-modulatory activity by High-Content Screening (HCS). We discovered a very strong HIV-1 inhibition mainly in samples taken from fjords with a strong terrestrial input. Multivariate data integration demonstrated an association of a set of polyphenols with specific biological alterations (endoplasmic reticulum, lysosomes, and NFkB) caused by these samples. Moreover, we found strong HIV-1 inhibition in one unrelated oceanic sample closely matching to HIV-1-inhibitory drugs on a cytological and a chemical level. Taken together, we demonstrate that even without physical purification, a sophisticated strategy of differential filtering, correlation analysis, and multivariate statistics can be employed to guide chemical analysis, to improve de-replication, and to identify ecosystems with promising characteristics as sources for NP discovery.
AB - Natural products (NP) are a valuable drug resource. However, NP-inspired drug leads are declining, among other reasons due to high re-discovery rates. We developed a conceptual framework using the metabolic fingerprint of entire ecosystems (MeE) to facilitate the discovery of global bioactivity hotspots. We assessed the MeE of 305 sites of diverse aquatic ecosystems, worldwide. All samples were tested for antiviral effects against the human immunodeficiency virus (HIV), followed by a comprehensive screening for cell-modulatory activity by High-Content Screening (HCS). We discovered a very strong HIV-1 inhibition mainly in samples taken from fjords with a strong terrestrial input. Multivariate data integration demonstrated an association of a set of polyphenols with specific biological alterations (endoplasmic reticulum, lysosomes, and NFkB) caused by these samples. Moreover, we found strong HIV-1 inhibition in one unrelated oceanic sample closely matching to HIV-1-inhibitory drugs on a cytological and a chemical level. Taken together, we demonstrate that even without physical purification, a sophisticated strategy of differential filtering, correlation analysis, and multivariate statistics can be employed to guide chemical analysis, to improve de-replication, and to identify ecosystems with promising characteristics as sources for NP discovery.
UR - http://www.scopus.com/inward/record.url?scp=85078501953&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-57709-0
DO - 10.1038/s41598-020-57709-0
M3 - Article
C2 - 31992728
AN - SCOPUS:85078501953
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 1319
ER -
