Total synthesis and functional evaluation of IORs, sulfonolipid-based inhibitors of cell differentiation in Salpingoeca rosetta.

Raguž L, Peng CC, Rutaganira FUN, Krüger T, Stanišić A, Jautzus T, Kries H, Kniemeyer O, Brakhage AA, King N, Beemelmanns C (2022) Total synthesis and functional evaluation of IORs, sulfonolipid-based inhibitors of cell differentiation in Salpingoeca rosetta. Angew Chem Int Ed 61(41), e202209105.

Abstract

The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular and scalable synthesis of sulfonolipid IOR-1A (six steps, 27% overall yield), which acts as bacterial inhibitor of rosette formation in S. rosetta . The synthesis features a decarboxylative cross-coupling reaction of a sulfonic acid-containing tartaric acid derivative with alkyl zinc reagents. Synthesis of 15 modified IOR-1A derivatives, including fluorescent and photoaffinity-based probes, allowed quantification of IOR-1A, localization studies within S. rosetta cells and evaluation of structure-activity relations. In a proof of concept study, an inhibitory bifunctional probe was employed in proteomic profiling studies, which allowed to deduce binding partners in bacteria and S. rosetta . These results showcase the power of synthetic chemistry to decipher the biochemical basis of cell differentiation processes within S. rosetta .

Leibniz-HKI-Autor*innen

Christine Beemelmanns
Axel A. Brakhage
Theresa Jautzus
Olaf Kniemeyer
Hajo Kries
Thomas Krüger
Chia-Chi Peng
Luka Raguž
Aleksa Stanišić

Identifier

doi: 10.1002/anie.202209105

PMID: 35901418