ERA-NET: Replacing food-competing feedstocks with Methanol, CO2 and Methylamine for a Sustainable Bioeconomy

I MCM4SB-prosjekt samarbeidet vi med internasjonale institusjoner fra Tyrkia (Marmara Universitet), Tyskland (Bielefeld Universitet) og Danmark (Aarhus Universitet), samt en industriell partner fra Slovenia (Acies Bio). Målet med samarbeidsprosjektet har vært å erstatte sukkerbaserte råmaterialer for mikrobielle bioprosesser i industriell bioteknologi, med mere bærekraftige én-karbon (C1) forbindelsene metanol, karbondioksid (CO2) og metylamin. Det langsiktige målet med forskningen er å etablere en bærekraftig produksjon av kjemikalier innenfor en bioøkonomi med lav bruk av fossilt brensel. Metanol kan produseres bærekraftig fra CO2, mens metylamin er en kopmponent som finnes i fiskeavfall og andre grønne kilder. Prosjektet integrerte metoder fra system biologi og syntetisk biologi for å konstruere nye bakteriestammer som er i stand til å vokse på metanol (dvs. metylotrofe) og som også kan inkorporere CO2 og metylamin for å produsere de organiske syrene fumarat, malat, samt aminosyrene tryptofan og putrescin. Alle disse er komersielle produkter. Vi diskuterte den vitenskapelige utviklingen i vårt siste møte i Trondheim, der både fortsatt ferdigstillelse av vitenskapelige publikasjoner og prosjektets bærekraft var tematikk. Videre spiller den tekno-økonomiske vurderingen en sentral rolle i å utforme bærekraftig bioprosessdesign, evaluere økonomisk gjennomførbarhet, identifisere flaskehalser, sette operasjonelle mål for prosessforbedring samt å fremheve potensielle avveininger i de første stadiene av design og utvikling. I tillegg er samfunnansvarlig forskning og innovasjon (RRI) en sentral og integrert forskningskomponent i MCM4SB, som prioriterer bærekraftig bioøkonomi forankret i fornybare råstoffer.

Given the growing global population and the urgent need for sustainable alternatives to sugar-based feedstocks in biotechnology, MCM4SB aimed to develop methanol-based bioprocesses using methylamine and CO2 to produce value-added chemicals like L-malate and N-methyl-L-glutamate. This initiative supports greener technologies through research and innovation. In this multidisciplinary collaboration, the project delivered biological materials (novel engineered strains), technology (novel genetic deletion tools), bio-based products (methanol- and CO2- derived organic and amino acids), and processes for industrial application (a novel model for methanol-based malate bioprocess). Over ten graduate students were recruited in NTNU and co-supervised across partner institutions, promoting professional and cultural exchange. This project presents the groundwork for future transnational collaborations and funding opportunities. Communication and dissemination are central to MCM4SB, with findings shared through peer-reviewed papers, conferences, and stakeholder meetings. Industry partners, especially Acies Bio, facilitate knowledge transfer, exemplified by an upcoming patent application. These efforts address societal challenges by creating alternatives to petroleum-based chemical industries.

The MCM4SB project aims to replace sugar-based feedstocks for bioprocesses with one carbon (C1) compounds, namely methanol (CH3OH), carbon dioxide (CO2) and methylamine (CH3NH2) in order to establish a novel, sustainable production within a low-fossil-fuel bio-economy. We will combine utilization of methanol with CO2 and/or methylamine for production of the bulk chemical L-malate and the specialty chemical N-methyl-L-glutamate, by using two different methylotrophic organisms Bacillus methanolicus and Methylobacterium extorquens. The application of two diverse hosts has a double impact on the establishment of novel biotechnological processes – on the metabolic engineering level, different genetic targets will be selected based on the flux balance analysis and on the technological level, different cultivation conditions such as medium components and temperature. B. methanolicus utilizes ribulose monophosphate cycle to assimilate methanol and is not able to use methylamine as carbon source while M. extorquens utilizes methylamine via the N-methyl-L glutamate pathway. This project combines systems and synthetic biology approaches. Specifically, target identification for strain development will be guided by the genome-scale metabolic models, which will be iteratively fine-tuned based on experimental test results, and the newly developed strains will be characterized on the transcriptome level in order to detect the bottlenecks in the metabolism, which will subsequently be relieved to steer the next round of strain development. The techno-economic assessment will help to steer the bioprocess design by assessing the economic feasibility, bottlenecks, and operation targets for process improvement and identify possible trade-offs during early stages of design and development. Responsible Research and Innovation will be a cross-cutting and integrated research activity in MCM4SB with a focus on sustainable bioeconomy based on renewable feedstocks.