Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308017810> ?p ?o ?g. }
- W4308017810 abstract "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." @default.
- W4308017810 created "2022-11-07" @default.
- W4308017810 creator A5005159928 @default.
- W4308017810 creator A5029372972 @default.
- W4308017810 creator A5032809831 @default.
- W4308017810 creator A5040032635 @default.
- W4308017810 creator A5060769915 @default.
- W4308017810 creator A5070962482 @default.
- W4308017810 creator A5083688078 @default.
- W4308017810 creator A5090542919 @default.
- W4308017810 date "2022-12-21" @default.
- W4308017810 modified "2023-10-07" @default.
- W4308017810 title "Enhanced Rishirilide Biosynthesis by a Rare In-Cluster Phosphopantetheinyl Transferase in Streptomyces xanthophaeus" @default.
- W4308017810 cites W1697776510 @default.
- W4308017810 cites W1968984443 @default.
- W4308017810 cites W1971598639 @default.
- W4308017810 cites W1976113843 @default.
- W4308017810 cites W1977482735 @default.
- W4308017810 cites W1979951818 @default.
- W4308017810 cites W1991828083 @default.
- W4308017810 cites W1995808589 @default.
- W4308017810 cites W2002543505 @default.
- W4308017810 cites W2012004265 @default.
- W4308017810 cites W2014680208 @default.
- W4308017810 cites W2018511557 @default.
- W4308017810 cites W2027609269 @default.
- W4308017810 cites W2058438531 @default.
- W4308017810 cites W2059466614 @default.
- W4308017810 cites W2068162139 @default.
- W4308017810 cites W2085584322 @default.
- W4308017810 cites W2095990743 @default.
- W4308017810 cites W2105199251 @default.
- W4308017810 cites W2110218116 @default.
- W4308017810 cites W2141193327 @default.
- W4308017810 cites W2155028909 @default.
- W4308017810 cites W2168974130 @default.
- W4308017810 cites W2256756668 @default.
- W4308017810 cites W2320487061 @default.
- W4308017810 cites W2376573086 @default.
- W4308017810 cites W2404280981 @default.
- W4308017810 cites W2409930878 @default.
- W4308017810 cites W2571989678 @default.
- W4308017810 cites W2792544439 @default.
- W4308017810 cites W2793787203 @default.
- W4308017810 cites W2808582716 @default.
- W4308017810 cites W2884519714 @default.
- W4308017810 cites W2884683306 @default.
- W4308017810 cites W2894479533 @default.
- W4308017810 cites W2910186643 @default.
- W4308017810 cites W2941342985 @default.
- W4308017810 cites W2942829220 @default.
- W4308017810 cites W2949721890 @default.
- W4308017810 cites W2950278155 @default.
- W4308017810 cites W2956233383 @default.
- W4308017810 cites W3011567137 @default.
- W4308017810 cites W3019768167 @default.
- W4308017810 cites W3100584158 @default.
- W4308017810 cites W3132901807 @default.
- W4308017810 cites W3157006267 @default.
- W4308017810 cites W3177828909 @default.
- W4308017810 doi "https://doi.org/10.1128/spectrum.03247-22" @default.
- W4308017810 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36326495" @default.
- W4308017810 hasPublicationYear "2022" @default.
- W4308017810 type Work @default.
- W4308017810 citedByCount "4" @default.
- W4308017810 countsByYear W43080178102022 @default.
- W4308017810 countsByYear W43080178102023 @default.
- W4308017810 crossrefType "journal-article" @default.
- W4308017810 hasAuthorship W4308017810A5005159928 @default.
- W4308017810 hasAuthorship W4308017810A5029372972 @default.
- W4308017810 hasAuthorship W4308017810A5032809831 @default.
- W4308017810 hasAuthorship W4308017810A5040032635 @default.
- W4308017810 hasAuthorship W4308017810A5060769915 @default.
- W4308017810 hasAuthorship W4308017810A5070962482 @default.
- W4308017810 hasAuthorship W4308017810A5083688078 @default.
- W4308017810 hasAuthorship W4308017810A5090542919 @default.
- W4308017810 hasBestOaLocation W43080178101 @default.
- W4308017810 hasConcept C104317684 @default.
- W4308017810 hasConcept C143065580 @default.
- W4308017810 hasConcept C16318435 @default.
- W4308017810 hasConcept C2777157883 @default.
- W4308017810 hasConcept C2777379556 @default.
- W4308017810 hasConcept C2777763344 @default.
- W4308017810 hasConcept C2778635478 @default.
- W4308017810 hasConcept C2779920670 @default.
- W4308017810 hasConcept C2780786045 @default.
- W4308017810 hasConcept C36857842 @default.
- W4308017810 hasConcept C523546767 @default.
- W4308017810 hasConcept C54355233 @default.
- W4308017810 hasConcept C553450214 @default.
- W4308017810 hasConcept C55493867 @default.
- W4308017810 hasConcept C86803240 @default.
- W4308017810 hasConceptScore W4308017810C104317684 @default.
- W4308017810 hasConceptScore W4308017810C143065580 @default.
- W4308017810 hasConceptScore W4308017810C16318435 @default.
- W4308017810 hasConceptScore W4308017810C2777157883 @default.
- W4308017810 hasConceptScore W4308017810C2777379556 @default.
- W4308017810 hasConceptScore W4308017810C2777763344 @default.
- W4308017810 hasConceptScore W4308017810C2778635478 @default.
- W4308017810 hasConceptScore W4308017810C2779920670 @default.