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Background   Lipomyces starkeyi  has been widely regarded as a promising oleaginous yeast with broad industrial application prospects because of its wide substrate spectrum, good adaption to fermentation inhibitors, excellent fatty acid composition for high-quality biodiesel, and negligible lipid remobilization. However, the currently low experimental lipid yield of  L. starkeyi  prohibits its commercial success. Metabolic model is extremely valuable to comprehend the complex biochemical processes and provide great guidance for strain modification to facilitate the lipid biosynthesis.    Results  A small-scale metabolic model of  L. starkeyi  NRRL Y-11557 was constructed based on the genome annotation information. The theoretical lipid yields of glucose, cellobiose, xylose, glycerol, and acetic acid were calculated according to the flux balance analysis (FBA). The optimal flux distribution of the lipid synthesis showed that pentose phosphate pathway (PPP) independently met the necessity of NADPH for lipid synthesis, resulting in the relatively low lipid yields. Several targets (NADP-dependent oxidoreductases) beneficial for oleaginicity of  L. starkeyi  with significantly higher theoretical lipid yields were compared and elucidated. The combined utilization of acetic acid and other carbon sources and a hypothetical reverse β-oxidation (RBO) pathway showed outstanding potential for improving the theoretical lipid yield.    Conclusions  The lipid biosynthesis potential of  L. starkeyi  can be significantly improved through appropriate modification of metabolic network, as well as combined utilization of carbon sources according to the metabolic model. The prediction and analysis provide valuable guidance to improve lipid production from various low-cost substrates.    Supplementary Information  The online version contains supplementary material available at 10.1186/s13068-021-01997-9.

A metabolic model of Lipomyces starkeyi for predicting lipogenesis potential from diverse low-cost substrates