Efficient production of itaconic acid from the single-carbon substrate methanol with engineered Komagataella phaffii
Manja Mølgaard Severinsen, Simone Bachleitner, Viola Modenese, Özge Ata, Diethard Mattanovich
Abstract
Abstract Background Amidst 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 CO 2 , represent promising substrates for biotechnological applications. Especially, methanol is gaining prominence for bio-production of commodity chemicals. Results In this study, we show the potential of Komagataella phaffii as a production platform for itaconic acid using methanol as the carbon source. Successful integration of heterologous genes from Aspergillus terreus ( cadA , mttA and mfsA ) alongside fine-tuning of the mfsA gene expression, led to promising initial itaconic acid titers of 28 g·L −1 after 5 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 −1 after less than 5 days of methanol feed, while increasing the product yield on methanol from 0.06 g·g −1 to 0.24 g·g −1 . Conclusion Our results highlight the potential of K. phaffii as a methanol-based platform organism for sustainable biochemical production.