The chromodepsins - chemistry, biology and biosynthesis of a selective Gq inhibitor natural product family.

Covering: up to April 2021The bacterial cyclic depsipeptides FR900359 (FR) and YM-254890 (YM) were shown to selectively inhibit Gαq proteins with high potency and selectivity and have recently emerged as valuable pharmacological tools due to their effective mechanism of action. Here, we summarize important aspects of this small and specialized natural product family, for which we propose the name chromodepsins, starting from their discovery, producing organisms and structural variety. We then review biosynthesis, structure-activity relationships and ecological and evolutionary aspects of the chromodepsins.

Thioesterase-mediated side chain transesterification generates potent Gq signaling inhibitor FR900359.

The potent and selective Gq protein inhibitor depsipeptide FR900359 (FR), originally discovered as the product of an uncultivable plant endosymbiont, is synthesized by a complex biosynthetic system comprising two nonribosomal peptide synthetase (NRPS) assembly lines. Here we characterize a cultivable bacterial FR producer, enabling detailed investigations into biosynthesis and attachment of the functionally important FR side chain. We reconstitute side chain assembly by the monomodular NRPS FrsA and the non-heme monooxygenase FrsH, and characterize intermolecular side chain transesterification to the final macrocyclic intermediate FR-Core, mediated by the FrsA thioesterase domain.

Macroalgal-bacterial interactions: Role of dimethylsulfoniopropionate in microbial gardening by Ulva (Chlorophyta).

The marine macroalga Ulva mutabilis (Chlorophyta) develops into callus-like colonies consisting of undifferentiated cells and abnormal cell walls under axenic conditions. Ulva mutabilis is routinely cultured with two bacteria, the Roseovarius sp. MS2 strain and the Maribacter sp.

Antibiotic-producing symbionts dynamically transition between plant pathogenicity and insect-defensive mutualism.

Pathogenic and mutualistic bacteria associated with eukaryotic hosts often lack distinctive genomic features, suggesting regular transitions between these lifestyles. Here we present evidence supporting a dynamic transition from plant pathogenicity to insect-defensive mutualism in symbiotic Burkholderia gladioli bacteria. In a group of herbivorous beetles, these symbionts protect the vulnerable egg stage against detrimental microbes.