Hybrid Chemoenzymatic Synthesis of C -Sugars for Molecular Evidence of in vivo Shikimate Pathway Inhibition.

The design of distinctive chemical synthesis strategies aims for the most efficient routes towards versatile compounds in drug target studies. Here, we establish a powerful hybrid synthetic approach of total chemical and chemoenzymatic synthesis to efficiently obtain various 7-deoxy-sedoheptulose (7dSh, 1) analogues, unique C sugars, for structure-activity relationship studies. 7dSh (1) is a rare microbial sugar with in planta herbicidal activity.

A bioactive molecule made by unusual salvage of radical SAM enzyme byproduct 5-deoxyadenosine blurs the boundary of primary and secondary metabolism.

5-Deoxyadenosine (5dAdo) is the byproduct of many radical S-adenosyl-l-methionine enzyme reactions in all domains of life. 5dAdo is also an inhibitor of the radical S-adenosyl-l-methionine enzymes themselves, making it necessary for cells to construct pathways to recycle or dispose of this toxic metabolite. However, the specific pathways involved have long remained unexplored.

Cyanobacterial antimetabolite 7-deoxy-sedoheptulose blocks the shikimate pathway to inhibit the growth of prototrophic organisms.

Antimetabolites are small molecules that inhibit enzymes by mimicking physiological substrates. We report the discovery and structural elucidation of the antimetabolite 7-deoxy-sedoheptulose (7dSh). This unusual sugar inhibits the growth of various prototrophic organisms, including species of cyanobacteria, Saccharomyces, and Arabidopsis.