Efficient production of itaconic acid from the single carbon substrate methanol with engineeredKomagataella phaffii

Abstract

AbstractBackgroundAmidst the escalating carbon dioxide levels resulting from fossil fuel consumption, there is a pressing need for sustainable, bio-based alternatives to underpin future global economies. Single carbon feedstocks, derived from CO2, represent promising substrates for biotechnological applications. Especially methanol is gaining prominence for bio-production of commodity chemicals.ResultsIn this study, we show the potential ofKomagataella phaffiias a production platform for itaconic acid using methanol as the carbon source. Successful integration of heterologous genes fromAspergillus terreus(cadA,mttAandmfsA) alongside fine-tuning of themfsAgene expression, led to promising initial itaconic acid titers of 28 g·L-1after five days of fed-batch cultivation. Through the combined efforts of process optimization and strain engineering strategies we further boosted the itaconic acid production reaching titers of 55 g·L-1after less than five days of methanol feed, whilst increasing the product yield on methanol from 0.06 g·g-1to 0.24 g·g-1.ConclusionOur results highlight the potential ofK. phaffiias a methanol-based platform organism for sustainable biochemical production.