Streptomyces xanthophaeus
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ABSTRACT:
PROVIDER: PRJNA735883 | ENA |
REPOSITORIES: ENA
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Project description:Discovery of a Dedicated PPTase to the Rishirilide Biosynthesis in Streptomyces xanthophaeus no2
| PRJNA735918 | ENA
Project description:Phosphopantetheinyl transferases (PPTases) play important roles in activating apo-acyl carrier proteins (apo-ACPs) and apo-peptidyl carrier proteins (apo-PCPs) in both primary and secondary metabolism. PPTases catalyze the posttranslational modifications of those carrier proteins by covalent attachment of the 4'-phosphopantetheine group to a conserved serine residue. The protein-protein interactions between a PPTase and a cognate acyl or peptidyl carrier protein have important regulatory functions in microbial biosynthesis, but the molecular mechanism underlying their specific recognition remains elusive. In this study, we identified a new rishirilide biosynthetic gene cluster with a rare in-cluster PPTase from Streptomyces xanthophaeus no2. The function of this Sfp-type PPTase, SxrX, in rishirilide production was confirmed using genetic mutagenesis and biochemical characterization. We applied molecular modeling and site-directed mutagenesis to identify key residues mediating the protein-protein interaction between SxrX and its cognate ACP. In addition, six natural products were isolated from wild-type S. xanthophaeus no2 and the ΔsxrX mutant, including rishirilide A and lupinacidin A, that exhibited antimicrobial and anticancer activities, respectively. SxrX is the first Sfp-type PPTase identified from an aromatic polyketide biosynthetic gene cluster and shown to be responsible for high-level production of rishirilide derivatives. IMPORTANCE Genome mining has been a vital means for natural product drug discovery in the postgenomic era. The rishirilide-type polyketides have attracted attention due to their potent bioactivity, but the poor robustness of production hosts has limited further research and development. This study not only identifies a hyperproducer of rishirilides but also reveals a rare, in-cluster PPTase SxrX that plays an important role in boosting rishirilide biosynthesis. Experimental and computational investigations revealed new insights on the protein-protein interaction between SxrX and its cognate ACP with wide implications for understanding polyketide biosynthesis.
| S-EPMC9769936 | biostudies-literature
Project description:Streptomyces xanthophaeus strain:KPP03845 Genome sequencing
| PRJNA923126 | ENA
Project description:Streptomyces xanthophaeus strain:A54 Genome sequencing
| PRJNA1205882 | ENA
Project description:Streptomyces xanthophaeus NBRC 12829 genome sequencing project
| PRJDB9815 | ENA
Project description:Streptomyces sp. AM6-12 Genome sequencing
| PRJNA1161424 | ENA
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| PRJNA363950 | ENA
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| PRJNA430076 | ENA
Project description:Streptomyces sp. ADI98-12 Genome sequencing and assembly
| PRJNA503729 | ENA