Biosynthesis of the Pipecolate Moiety of Marcfortine A

• Published in: Journal of the American Chemical Society Vol. 121; no. 9; pp. 1763 - 1767
• Main Authors: Kuo, M. S, Yurek, D. A, Mizsak, S. A, Cialdella, J. I, Baczynskyj, L, Marshall, V. P
• Format: Journal Article
• Language: English
• Published: American Chemical Society 10.03.1999
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja983128d

In this paper, we demonstrate that the marcfortine A (MA) producing Penicillium strain incorporates l-lysine, which is metabolized to the pipecolate moiety by losing the α-amino group and not the ε-amino group as determined by employing [α-15N]- or [ε-15N]-l-lysine in our feeding study. Each of the enriched samples was analyzed by FAB-MS and a number of NMR experiments. The analysis of the 1H NMR spectrum allowed us to estimate the absolute enrichment of the amide nitrogen (Nβ). Analysis of HMBC spectra allowed us to establish the relative enrichments of the other two nitrogens to Nβ. To the best of our knowledge, this represents the first time that results from an HMBC experiment have been used to quantitate the relative enrichment of an isotope. The agreement between NMR results and the FAB-MS are excellent, further supporting our conclusions. The knowledge of the specific loss of the α-amino group allows the differentiation of two plausible pathways in converting l-lysine to pipecolic acid.