Heterologous reconstitution in yeast of the polyunsaturated fatty acid biosynthetic pathway

A Caenorhabditis elegans ORF encoding the presumptive condensing enzyme act ivity of a fatty acid elongase has been characterized functionally by heter ologous expression in yeast. This ORF (F56H 11.4) shows low similarity to S accharomyces cerevisiae genes involved in fatty acid elongation. The substr ate specificity of the C. elegans enzyme indicated a preference for Delta(6 )-desaturated C18 polyunsaturated fatty acids. Coexpression of this activit y with fatty acid desaturases required for the synthesis of C20 polyunsatur ated fatty acids resulted in the accumulation of arachidonic acid from lino leic acid and eicosapentaenoic acid from alpha-linolenic acid. These result s demonstrate the reconstitution of the n-3 and n-6 polyunsaturated fatty a cid biosynthetic pathways. The C. elegans ORF is likely to interact with en dogenous components of a yeast elongation system, with the heterologous nem atode condensing enzyme F56H11.4 causing a redirection of enzymatic activit y toward polyunsaturated C18 fatty acid substrates.