Biosynthesis of Antibiotics of the Virginiamycin Family, 6. Biosynthesis of Virginiamycin S<sub>1</sub>

Molinero, Anthony A.; Kingston, David G. I.; Reed, Josephine W.

doi:10.1021/np50061a013

Cited by 15 publications

(9 citation statements)

References 43 publications

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“…Virginiamycin S, a cyclohexadepsipeptide antibiotic, has two unusual amino acid residues, 4-oxopipecolic acid, and 3-hydroxypicolinic acid [30,31]. Both amino acids are originally derived from lysine [32], and the first steps in the biogenesis of these two amino acids are presumably the same: cyclization of L-lysine with loss of a-nitrogen [33]. Two genes that have been identified in the virginiamycin biosynthetic gene cluster could be responsible for this reaction: visC encoding a cyclodeaminase similar to RapL, and visA encoding a L-lysine 2-maminotransferase with high homology to NikC [29].…”

Section: Lysine Cyclodeamination Pathwaymentioning

confidence: 99%

Pipecolic acid in microbes: biosynthetic routes and enzymes

2006

J IND MICROBIOL BIOTECHNOL

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Pipecolic acid is an important precursor of many useful microbial secondary metabolites. Pipecolic acid-derived moieties are often crucial for the biological activities of some microbial natural products with pharmaceutical applications. Understanding the biogenesis of pipecolic acid in microorganisms would be a significant step toward the mutasynthesis of novel analogs of choice. This review focuses on various microbial pathways and enzymes for pipecolic acid synthesis, especially those related to the origination of pipecolic acid moieties in secondary metabolites.

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Section: Lysine Cyclodeamination Pathwaymentioning

confidence: 99%

Pipecolic acid in microbes: biosynthetic routes and enzymes

2006

J IND MICROBIOL BIOTECHNOL

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“…The biosynthesis of the unusual amino acids that comprise type B streptogramins has not been extensively studied. Labeled precursor feeding experiments have shown that phenylalanine is the source of phenylglycine 29,30 and both 4-oxopipecolic acid and 3-hydroxypicolinic acid are derived from Lys 30,31 during the biosynthesis of virginiamycin S 1 by Streptomyces virginiae. A four-gene system for the production of 4-N,N-(dimethylamino)-L-Phe has been cloned and partially characterized from the pristinamycin producer Streptomyces pristinaespiralis.…”

Section: Structures and Biosynthesismentioning

confidence: 99%

Streptogramins, Oxazolidinones, and Other Inhibitors of Bacterial Protein Synthesis

2005

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“…PI A biosynthesis could be schematically divided in three parts: precursor production, branched cyclohexadepsipeptide synthesis, and final macrocycle modifications. In this respect, incorporation studies of precursors labeled with radioactive or stable isotopes have provided insight into how the uncommon amino acid and chromophore residues of virginiamycin S 1 , a PI A analog having a ␣N-methyl-L-phenylalanine as residue 5, are built (22,27,28). More recently, isolation and characterization of a cluster of pap genes (3,5,6) led to a proposal for an L-DMPAPA biosynthetic pathway starting from chorismic acid.…”

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confidence: 99%

Purification of peptide synthetases involved in pristinamycin I biosynthesis

et al. 1997

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Several assays of pristinamycin I synthetases based on adenylate or thioester formation were developed. Purification to near homogeneity of these enzymatic activities from cell extracts of Streptomyces pristinaespiralis showed that three enzymes could activate all pristinamycin I precursors. SnbA, a 3-hydroxypicolinic acid: AMP ligase activating the first pristinamycin I residue, was purified 200-fold, using an ATP-pyrophosphate exchange assay. This enzyme was shown to be a monomer with an M r of 67,000 as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Then a multifunctional enzyme, consisting of two identical subunits (SnbC) with M r s of 240,000 and able to bind covalently L-threonine as a thioester, was purified 100-fold. This protein also activated L-aminobutyric acid, which is further epimerized to generate the third residue of the pristinamycin I macrocycle. A third protein, consisting of two identical subunits (SnbD) with M r s estimated to be between 250,000 and 350,000, was purified 200-fold. This large enzyme catalyzed thioesterification and subsequent N-methylation of 4-dimethylamino-L-phenylalanine, the fifth pristinamycin I residue. SnbD could also activate L-proline, the fourth pristinamycin I residue, and some preparations retained a low but significant activity for the last two pristinamycin I precursors. Finally, a single polypeptide chain (SnbE) with an M r of 170,000, catalyzing L-phenylglycine-dependent ATP-pyrophosphate exchange, was purified 3,000-fold and characterized. Stepwise Edman degradation of the entire polypeptides or some of their internal fragments provided amino acid sequences for the four isolated proteins. The purified SnbE protein was further shown to be a proteolytic fragment of SnbD.

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Biosynthesis of Antibiotics of the Virginiamycin Family, 6. Biosynthesis of Virginiamycin S₁

Cited by 15 publications

References 43 publications

Pipecolic acid in microbes: biosynthetic routes and enzymes

Pipecolic acid in microbes: biosynthetic routes and enzymes

Streptogramins, Oxazolidinones, and Other Inhibitors of Bacterial Protein Synthesis

Purification of peptide synthetases involved in pristinamycin I biosynthesis

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Biosynthesis of Antibiotics of the Virginiamycin Family, 6. Biosynthesis of Virginiamycin S1

Cited by 15 publications

References 43 publications

Pipecolic acid in microbes: biosynthetic routes and enzymes

Pipecolic acid in microbes: biosynthetic routes and enzymes

Streptogramins, Oxazolidinones, and Other Inhibitors of Bacterial Protein Synthesis

Purification of peptide synthetases involved in pristinamycin I biosynthesis

Contact Info

Product

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Biosynthesis of Antibiotics of the Virginiamycin Family, 6. Biosynthesis of Virginiamycin S₁