prunustatin-a and neoantimycin

Cloning natural product biosynthetic gene clusters from cultured or uncultured sources and their subsequent expression by genetically tractable heterologous hosts is an essential strategy for the elucidation and characterisation of novel microbial natural products. The availability of suitable expression hosts is a critical aspect of this workflow. In this work, we mutagenised five endogenous biosynthetic gene clusters from Streptomyces albus S4, which reduced the complexity of chemical extracts generated from the strain and eliminated antifungal and antibacterial bioactivity. We showed that the resulting quintuple mutant can express foreign biosynthetic gene clusters by heterologously producing actinorhodin, cinnamycin and prunustatin. We envisage that our strain will be a useful addition to the growing suite of heterologous expression hosts available for exploring microbial secondary metabolism.

Topics: Anthraquinones; Bacteriocins; Biological Products; Cloning, Molecular; Gene Expression Regulation, Bacterial; Macrolides; Molecular Structure; Organic Chemicals; Peptides, Cyclic; Species Specificity; Streptomyces

In the course of our screening program for regulators of a molecular chaperone GRP78 expression, we isolated a novel inhibitor of GRP78 expression, designated as prunustatin A, from Streptomyces violaceoniger 4521-SVS3. The planar structure of prunustatin A was determined to be an oxidized type of the neoantimycin family. Its absolute stereochemistry was established to be 2R, 4S, 6S, 7R, 9S, and 29S by analyzing chemically degraded components obtained from the derivative of prunustatin A.

Topics: Endoplasmic Reticulum Chaperone BiP; Glucose; Heat-Shock Proteins; Humans; Macrolides; Molecular Chaperones; Molecular Structure; Organic Chemicals; Peptides, Cyclic; Stereoisomerism; Streptomyces; Tumor Cells, Cultured