Metabolic profiling and flux distributions reveal a key role of acetyl-CoA in sophorolipid synthesis by Candida bombicola

Abstract

Sophorolipids are important biosurfactants produced by the wild-type strain of Candida bombicola ATCC 22214, with antimicrobial, antiviral, and anticancer activities. Our previous study showed that a mutant strain lacking multifunctional enzyme type 2 displayed extremely low sophorolipid production capacity compared to the wild-type strain. In the present study, we aimed to reveal the possible reasons for this deficiency through a series of analytical methods. First, comparative metabolic profiling analysis between the wild-type and mutant strains was performed. Multivariate statistical analysis, including principal component analysis and orthogonal partial least squares discriminant analysis, showed that nine potential metabolites were closely associated with the metabolic differences between strains. Second, metabolic flux analysis revealed that an inadequate supply of intracellular acetyl-CoA in the mutant strain could significantly affect the biosynthesis of sophorolipids. In addition, supplementation of citric acid recovered the sophorolipid production in the mutant strain by approximately 83%, suggesting that citrate metabolism plays an important role in sophorolipid biosynthesis. These findings provide novel theoretical insights for further improving the production of sophorolipids in C. bombicola.