TY - JOUR
T1 - Rapid, Selective, and Sensitive Method for Semitargeted Discovery of Congeneric Natural Products by Liquid Chromatography Tandem Mass Spectrometry
AU - Herath, Kithsiri B.
AU - Previs, Stephen F.
AU - Roddy, Thomas P.
AU - Attygalle, Athula B.
AU - González, Ignacio
AU - Genilloud, Olga
AU - Singh, Sheo B.
N1 - Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society and American Society of Pharmacognosy.
PY - 2021/3/26
Y1 - 2021/3/26
N2 - Natural product congeners serve a useful role in the understanding of natural product biosynthesis and structure-activity relationships. A minor congener with superior activity, selectivity, and modifiable functional groups could serve as a more effective lead structure and replace even the original lead molecule that was used for medicinal chemistry modifications. Currently, no effective method exists to discover targeted congeners rapidly, specifically, and selectively from producing sources. Herein, a new method based on liquid-chromatography tandem-mass spectrometry combination is evaluated for targeted discovery of congeners of platensimycin and platencin from the extracts of Streptomyces platensis. By utilizing a precursor-ion searching protocol, tandem mass spectrometry not only confirmed the presence of known congeners but also provided unambiguous detection of many previously unknown congeners of platensimycin and platencin. This high-throughput and quantitative method can be rapidly and broadly applied for dereplication and congener discovery from a variety of producing sources, even when the targeted compounds are obscured by the presence of unrelated natural products.
AB - Natural product congeners serve a useful role in the understanding of natural product biosynthesis and structure-activity relationships. A minor congener with superior activity, selectivity, and modifiable functional groups could serve as a more effective lead structure and replace even the original lead molecule that was used for medicinal chemistry modifications. Currently, no effective method exists to discover targeted congeners rapidly, specifically, and selectively from producing sources. Herein, a new method based on liquid-chromatography tandem-mass spectrometry combination is evaluated for targeted discovery of congeners of platensimycin and platencin from the extracts of Streptomyces platensis. By utilizing a precursor-ion searching protocol, tandem mass spectrometry not only confirmed the presence of known congeners but also provided unambiguous detection of many previously unknown congeners of platensimycin and platencin. This high-throughput and quantitative method can be rapidly and broadly applied for dereplication and congener discovery from a variety of producing sources, even when the targeted compounds are obscured by the presence of unrelated natural products.
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U2 - 10.1021/acs.jnatprod.0c01190
DO - 10.1021/acs.jnatprod.0c01190
M3 - Article
C2 - 33523676
AN - SCOPUS:85100758107
SN - 0163-3864
VL - 84
SP - 814
EP - 823
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 3
ER -