Lyngbyastatins

Lyngbyastatins 1 and 3 are cytotoxic cyclic depsipeptides that possess antiproliferative activity against human cancer cell lines.

[1] These compounds, first isolated from the extract of a Lyngbya majuscula/Schizothrix calcicola assemblage and from L. majuscula Harvey ex Gomont (Oscillatoriaceae) strains, respectively, target the actin cytoskeleton of eukaryotic cells.

An acyl unit from malonyl CoA is then coupled onto the initial substrate via an acyltransferase (AT) and then methylated at the alpha carbon through a C-methyltransferase (CMT) before an aminotransferase (AmT) conducts a transamination of the initial substrate carbonyl.

LbnB, a traditional NRPS, adds glycine into the growing thioester by its amino group.

NRPS LbnF completes the biosynthesis by coupling L-alanine before the thioesterase (TE) domain conducts a head-to-tail cyclization to produce the final depsipeptide products.

Proposed biosynthesis of lyngbyastatins 1 and 3. [ 1 ]