Sanyensin with an Unprecedented Architecture: An Effective Strategy from Discovery to Stereochemical Identification of Flexible Natural Products
Journal article, 2024

Under the guidance of genome mining combined with bioassay-coupled metabolomic analyses, an unprecedented macrodiolide sanyensin (1), with two flexible macrolides fused by the rigid oxabicyclo[3.3.1]nonane core, was isolated from the deep-sea-derived Streptomyces sp. OUCT16-30. The stereochemistry of 1 was established by NOEs (nuclear Overhauser effects), J-based configuration analysis, Marfey’s analysis, and together with a newly introduced stereochemical study workflow, which greatly shortens the time to obtain correct conformations of flexible structures based on the NMR constraints, thus leading to reliable quantum chemical calculations to establish the absolute configurations. This workflow is expected to have broad applicability for elucidating the stereochemistry of flexible natural products. The macrodiolide framework of 1 is proposed to be formed through a biocatalytic cyclodimerization, followed by a series of nonenzymatic reactions. This work leads to new insights into the unexplored biosynthetic potential of deep-sea microbes and also provides a practical streamline for efficient mining of novel natural products, from discovery to stereochemical finalization.

Author

Runyi Wang

Ocean University of China

Suling Xu

Ocean University of China

Di Su

Ocean University of China

Yilei Bao

Ocean University of China

Luyao Xu

Ocean University of China

Krister Holmberg

Chalmers, Chemistry and Chemical Engineering, Applied Chemistry

Qinggang Wang

Chinese Academy of Sciences

Huayue Li

Ocean University of China

Pilot National Laboratory for Marine Science and Technology (QNLM)

Analytical Chemistry

0003-2700 (ISSN) 1520-6882 (eISSN)

Vol. 96 42 16621-16628

Subject Categories (SSIF 2011)

Organic Chemistry

DOI

10.1021/acs.analchem.4c02567

More information

Latest update

4/14/2025