Discovery of unusual dimeric piperazyl cyclopeptides encoded by a DSM 44664 biosynthetic supercluster.

Rare actinomycetes represent an underexploited source of new bioactive compounds. Here, we report the use of a targeted metabologenomic approach to identify piperazyl compounds in the rare actinomycete Lentzea flaviverrucosa DSM 44664. These efforts to identify molecules that incorporate piperazate building blocks resulted in the discovery and structural elucidation of two dimeric biaryl-cyclohexapeptides, petrichorins A and B.

Construction of a new integrating vector from actinophage ϕOZJ and its use in multiplex Streptomyces transformation.

Streptomyces and other closely-related actinobacteria are important sources of bioactive molecules. Streptomyces synthetic biology and genetics empower therapeutic and agrichemical development through strain improvement and biosynthetic understanding. Such efforts rely on the availability of developed molecular toolsets.

Bioinformatic and Functional Evaluation of Actinobacterial Piperazate Metabolism.

Piperazate (Piz) is a nonproteinogenic amino acid noted for its unusual N-N bond motif. Piz is a proline mimic that imparts conformational rigidity to peptides. Consequently, piperazyl molecules are often bioactive and desirable for therapeutic exploration.

Draft Genome Sequence of sp. Strain JV178, a Producer of Clifednamide-Type Polycyclic Tetramate Macrolactams.

Here, we report the draft genome sequence of sp. JV178, a strain originating from Connecticut (USA) garden soil. This strain produces the polycyclic tetramate macrolactam compounds clifednamides A and B.

Engineered holocytochrome synthases that biosynthesize new cytochromes .

Cytochrome (cyt ), required for electron transport in mitochondria, possesses a covalently attached heme cofactor. Attachment is catalyzed by holocytochrome synthase (HCCS), leading to two thioether bonds between heme and a conserved CXXCH motif of cyt In cyt , histidine (His19) of CXXCH acts as an axial ligand to heme iron and upon release of holocytochrome from HCCS, folding leads to formation of a second axial interaction with methionine (Met81). We previously discovered mutations in human HCCS that facilitate increased biosynthesis of cyt in recombinant Focusing on HCCS E159A, novel cyt variants in quantities that are sufficient for biophysical analysis are biosynthesized.