- Targeted Rediscovery and Biosynthesis of the Farnesyl-Transferase Inhibitor Pepticinnamin E
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The natural product pepticinnamin E potently inhibits protein farnesyl transferases and has potential applications in treating cancer and malaria. Pepticinnamin E contains a rare N-terminal cinnamoyl moiety as well as several nonproteinogenic amino acids, including the unusual 2-chloro-3-hydroxy-4-methoxy-N-methyl-L-phenylalanine. The biosynthesis of pepticinnamin E has remained uncharacterized because its original producing strain is no longer available. Here we identified a gene cluster (pcm) for this natural product in a new producer, Actinobacteria bacterium OK006, by means of a targeted rediscovery strategy. We demonstrated that the pcm cluster is responsible for the biosynthesis of pepticinnamin E, a nonribosomal peptide/polyketide hybrid. We also characterized a key O-methyltransferase that modifies 3,4-dihydroxy-l-phenylalanine. Our work has identified the gene cluster for pepticinnamins for the first time and sets the stage for elucidating the unique chemistry required for biosynthesis.
- Santa Maria, Kevin C.,Chan, Andrew N.,O'Neill, Erinn M.,Li, Bo
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p. 1387 - 1393
(2019/05/15)
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- Synthesis of tyrosine derivatives for saframycin MX1 biosynthetic studies
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Saframycin MX1 and structural relatives are natural anticancer agents isolated from bacteria and marine invertebrates. For biosynthetic studies and to make a library of modified natural products, a series of tyrosine derivatives were synthesized in a conc
- Schmidt, Eric W.,Nelson, James T.,Fillmore, John P.
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p. 3921 - 3924
(2007/10/03)
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