TY  - BOOK
AU  - Ueoka,Reiko
AU  - Sondermann,Philipp
AU  - Leopold-Messer,Stefan
AU  - Liu,Yizhou
AU  - Suo,Rei
AU  - Bhushan,Agneya
AU  - Vadakumchery,Lida
AU  - Greczmiel,Ute
AU  - Yashiroda,Yoko
AU  - Kimura,Hiromi
AU  - Nishimura,Shinichi
AU  - Hoshikawa,Yojiro
AU  - Yoshida,Minoru
AU  - Oxenius,Annette
AU  - Matsunaga,Shigeki
AU  - Williamson,R.Thomas
AU  - Carreira,Erick M.
AU  - Piel,Jörn
TI  - Genome-based discovery and total synthesis of janustatins, potent cytotoxins from a plant-associated bacterium
PY  - 2022///-09-05
KW  - Text
KW  - local
N1  - /pmc/articles/PMC7613652; /pubmed/36064972
N2  - Host-associated bacteria are increasingly recognized as underexplored sources of bioactive natural products with unprecedented chemical scaffolds. A recently identified example is the plant root-associated marine bacterium Gynuella sunshinyii of the chemically underexplored order Oceanospirillales. Its genome contains at least 22 biosynthetic gene clusters suggesting a rich and mostly uncharacterized specialized metabolism. In this work, in silico chemical prediction of a non-canonical polyketide synthase cluster led to the discovery of janustatins, structurally unprecedented polyketide alkaloids with potent cytotoxicity that are produced at minute quantities. A combination of MS and 2D NMR experiments, density functional theory calculations of (13)C chemical shifts, and semiquantitative interpretation of T-ROESY data were conducted to determine the relative configuration, which enabled the total synthesis of both enantiomers and assignment of the absolute configuration. Janustatins feature a previously unknown pyridodihydropyranone heterocycle and an unusual biological activity consisting of delayed, synchronized cell death at subnanomolar concentrations
UR  - http://dx.doi.org/10.1038/s41557-022-01020-0
ER  -