Alternative routes of acetyl-CoA synthesis identified by comparative genomic analysis: involvement in the lipid production of oleaginous yeast and fungi.

For a bio-based economy, microbial lipids offer a potential solution as alternative feedstocks in the oleochemical industry. The existing genome data for the promising strains, oleaginous yeasts and fungi, allowed us to investigate candidate orthologous sequences that participate in their oleaginicity. Comparative genome analysis of the non-oleaginous (Saccharomyces cerevisiae, Candida albicans and Ashbya gossypii) and oleaginous strains (Yarrowia lipolytica, Rhizopus oryzae, Aspergillus oryzae and Mucor circinelloides) showed that 209 orthologous protein sequences of the oleaginous microbes were distributed over several processes of the cells. Based on the 41 sequences categorized by metabolism, putative routes potentially involved in the generation of precursors for fatty acid and lipid synthesis, particularly acetyl-CoA, were then identified that were not present in the non-oleaginous strains. We found a set of the orthologous oleaginous proteins that was responsible for the biosynthesis of this key two-carbon metabolite through citrate catabolism, fatty acid β-oxidation, leucine metabolism and lysine degradation. Our findings suggest a relationship between carbohydrate, lipid and amino acid metabolism in the biosynthesis of acetyl-CoA, which contributes to the lipid production of oleaginous microbes.