Microbial synthesis of biofuels offers a promising solution to the global environmental and energy concerns. However, the main challenge of microbial cell factories is their high fermentation costs. Model hosts, such as Escherichia coli and Saccharomyces cerevisiae, are typically used for proof-of-concept studies of producing different types of biofuels, however, they have a limited potential for biofuel production at an industrially relevant scale due to the weak stability/robustness and narrow substrate scope. With the advancements of synthetic biology and metabolic engineering, nonmodel eukaryotes, with naturally favorable phenotypic and metabolic features, have been emerging as promising biofuel producers. Here, we introduce the emerging nonmodel eukaryotes for the biofuel production and discuss their specific advantages, especially those with the capacity of producing cellulosic ethanol, higher alcohols, and fatty acid-/terpene-derived biofuel molecules. We also propose the challenges and prospects for developing nonmodel eukaryotic as the ideal hosts for future biofuel production.
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