BIOL 235 |
| Of interest to us is the carbon-phosphorus bond containing natural product, K-26. This potent angiotensin converting enzyme inhibitor is a naturally occurring N-acetylated tripeptide containing isoleucine, tyrosine and the non-proteinogenic amino acid (R)-1-amino-2-(4-hydroxyphenyl)ethyl phosphonic acid (AHEP). Stable isotopic incorporation studies with LC/MS analysis were employed to reveal the biosynthetic origin of AHEP and the mechanism of C-P bond formation. Isotopic incorporation experiments with labeled tyrosine clearly indicated AHEP is derived from tyrosine. Incorporation of synthetic 13C labeled AHEP revealed that AHEP is a discrete precursor of K-26 and C-P bond formation occurs before peptide coupling, suggesting a new C-P bond forming mechanism. Biochemical experiments with isoleucine, isoleucine-tyrosine, and isoleucine-tyrosine-AHEP provided evidence that acetylation occurs after all peptide couplings, setting the stage for further investigation of the K-26 biosynthetic pathway. Isolation and sequencing of biosynthetic enzymes will enable the identification of the K-26 biosynthetic gene cluster. |
|
Frontiers in Chemical Biology
5:00 PM-7:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biological Chemistry |