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Abstract By way of broadening the use of diverse sustainable bioethanol feedstocks, the potentials of Paper mulberry fruit juice (PMFJ), as a non-food, sugar-based substrate, were evaluated for fuel ethanol production. The suitability of PMFJ was proven, as maximum ethanol concentration (56.4 g/L) and yield (0.39 g/g) were achieved within half a day of the start of fermentation, corresponding to very high ethanol productivity of 4.7 g/L/hr. The established potentials were further optimally maximized through the response surface methodology (RSM). At the optimal temperature of 30 °C, yeast concentration of 0.55 g/L, and pH of 5, ethanol concentration, productivity, and yield obtained were 73.69 g/L, 4.61 g/L/hr, and 0.48 g/g, respectively. Under these ideal conditions, diverse metal salts were afterward screened for their effects on PMFJ fermentation. Based on a two-level fractional factorial design, nutrient addition had no positive impact on ethanol production. Thus, under the optimal process conditions, and without any external nutrient supplementation, bioethanol from PMFJ compared favorably with typical sugar-based energy crops, highlighting its resourcefulness as a high-value biomass resource for fuel ethanol production. Graphical Abstract