A novel, unique four-member protein family involved in extracellular fatty acid binding in Yarrowia lipolytica

Abstract

Abstract Background: Yarrowia lipolytica, a non-conventional oleaginous yeast species, has attracted attention due to its high lipid degradation and accumulation capacity. Y lipolytica is used as a chassis for the production of usual and unusual lipids and lipids derivatives. While genes involved in the intracellular transport and activation of fatty acids in the different cellular compartments have been characterized, no genes involved in fatty acid transport from the extracellular medium into the cell have been identified so far. In this study, we have identified secreted proteins involved in extracellular fatty acid binding.Results: The recent analysis of the Y. lipolytica secretome leads to the identification of a multi-gene family composed of four secreted proteins hereafter named UP1 to UP4. The protein products were efficiently over-expressed individually in native and multi-deletant strain (Q4: Δup1Δup2Δup3Δup4) backgrounds. Phenotype analysis demonstrated the involvement of those proteins in the binding of extracellular fatty acid. Also, deletion of these genes could prevent octanoic acid (C8) toxicity; while their individual over-expression increased sensitivity to its toxic action. The results suggested binding according to aliphatic chain length- and fatty acid concentration-dependent manner. 3D structure modelling supports at a molecular level their role in fatty acid accommodation.Conclusions: Extracellular fatty acid binding proteins were identified for the first time in Y. lipolytica. The new gene family names are proposed eFbp1 to eFbp4. The exact mode of eFbps action remains to be deciphered individually and synergistically, nevertheless, it is expected that the proteins may be relevant in lipid biotechnology, such as improving fatty acid production and/or bioconversion.