STUDIES ON THE BIOSYNTHESIS OF TAXOL - THE TAXANE CARBON SKELETON IS NOT OF MEVALONOID ORIGIN

A cell culture of Taxus chinensis was established to produce the diter pene 2 alpha,5 alpha,10 beta,14 beta-tetra-acetoxy-4(20),11-taxadiene (taxuyunnanine C) in 2.6% (dry weight) yield. The incorporation of [U- C-13(6)]glucose, [1-C-13]glucose, and [1,2-C-13(2)]acetate into this d iterpene was analyzed by NMR spectroscopy, Label from [1,2-C-13(2)]ace tate was diverted to the four acetyl groups of taxuyunnanine C, but no t to the taxane ring system, Label from [1-C-13]glucose and [U-C-13(6) ]glucose was efficiently incorporated into both the taxane ring system and the acetyl groups, The four isoprenoid moieties of the diterpene showed identical labeling patterns. The analysis of long-range C-13 C- 13 couplings in taxuyunnanine C obtained from an experiment with [U-C- 13(6)]glucose documents the involvement of an intramolecular rearrange ment in the biosynthesis of the isoprenoid precursor, The labeling pat terns are inconsistent with the mevalonate pathway, The taxoid data sh are important features with the alternative pathway of isoprenoid bios ynthesis operating in certain eubacteria [Rohmer, M., Knani, M., Simon in, P., Sutter, B. & Sahm, H. (1993) Biochem. J. 295, 517-524].