The cyclic depsipeptide FR900359 (FR, 1), a selective inhibitor of Gαq proteins (Ki= 6.90 ± 1.30nM), is applied as an extremely useful pharmacological tool. Additionally, this highly active molecule is evaluated for the treatment of pulmonary diseases and melanoma [1]. FR is present in the higher plant Ardisia crenata [2], which is known to harbor symbiotic bacteria of the genus Burkholderia [3,5]. In the current study, the novel, closely related cyclic depsipeptide AC-1 (2) was isolated as a minor metabolite from A. crenata. Structure elucidation was performed by extensive 2D-NMR and MS2 analysis. Despite only little structural differences in AC-1 as compared to FR (see figure below), its bioactivity towards Gαq proteins is altered. These findings together with results from the semi-synthetically derived FR-Hexanoate (3) allowed us to deduce first structure-activity-relationships. These cyclic depsipeptides show several structural peculiarities, (i) rare, non-proteinogenic amino acids with manifold N- and O-methylations, (ii) multiple ester bonds, and (iii) cis-configurated amide bonds [4], which makes their non-ribosomal and bacterial origin likely. Indeed, sequencing the genome of Candidatus Burkholderia crenata, the leaf nodule symbiont of A. crenata, revealed a non-ribosomal peptide synthetase (NRPS) gene cluster, putatively encoding FR biosynthesis.5 First results verified the deduced biosynthetic hypothesis and serve as basis for further genetic and biochemical studies.