Eugeni V. Entchev, Dominik Schwudke, Vitali Matyash, Bianca Abermann, Michaela Wilsch-Bruninger, Andrej Shevchenko and Teymuras V. Kurzchalia. Recently, metabolic studies in C.elegans are catching considerable attention. However, the small molecule products of many enzymes are not known. Generally in a genetic system such as C.elegans, these molecules can be identified based on two approaches: i) by analyzing metabolites in mutants; ii) by complementing mutants with downstream products. We have exploited these two approaches in order to study the function of
let-767, a short chain dehydrogenase/ reductase involved either in sterols or fatty acids metabolism. By complementing
let-767 (RNAi) developmental arrest with hydrophobic extract from wild type worms, we found that the critical missing products in
let-767 (RNAi) were the monomethyl branched chain fatty acids (mmBCFA). Consistently, the amount of mmBCFA in triacylglycerols from
let-767 (RNAi) worms was highly reduced. In addition, we studied the cellular requirements of LET-767 and showed that its activity was important for the apical structure of the intestinal cells. Thus, identification of the product of LET-767 allowed to connect its cellular functions with a class of lipids, products of this enzyme. Our combination of approaches can be used in order to study other metabolic enzymes.