Figure 1. Comparison of the previous model and the model supported by our current data.

In both the previous model (A) and the current model (B), long-chain ascarosides are shortened to medium- and short-chain ascarosides through β-oxidation cycles in the peroxisome. (A) According to the previous model, the final step in the biosynthesis of all of the IC-modified ascarosides is the attachment of the IC head group to the 4’-position of the ascarylose sugar. Short/medium-chain ascarosides, such as asc-C5 and asc-C9, are transported from the peroxisome to the lysosome, where the IC group is attached. According to this model, the acyl-CoA synthetase ACS-7 plays a key role in activating ICA as its corresponding CoA thioester, IC-CoA, for attachment specifically to asc-C5 to make IC-asc-C5. (B) According to our model, the IC head group is only attached to ascarosides with medium-length side chains, such as asc-C9. The biosynthesis of IC-modified ascarosides with shorter side chains, such as IC-asc-C5, requires additional β-oxidation in the peroxisome. In our model, under favorable conditions, the IC head group is attached by unknown enzymes to the medium-chain ascarosides, such as asc-C9, to make aggregation pheromones. This process may occur in the lysosome as it has been shown that the lysosome is required for the biosynthesis of 4’-modified ascarosides (Panda et al., 2017). If conditions decline, such as during starvation, ACS-7 then plays a key role for activating IC-asc-C9 as the corresponding CoA-thioester for further β-oxidation of its side chain in the peroxisome to make shorter-chain IC-ascarosides, such as the dauer pheromone IC-asc-C5.