South Dakota will be a national leader in use-inspired, machine learning-driven research in biological nitrogen fixation. This will be accomplished by incubating four research areas and developing a diverse BNF workforce. Our research goal is to obtain an ML-driven systematic understanding of genomic mechanisms associated with oxic N2-fixation in cyanobacteria and enable its application in sustainable agriculture and other industries. The initial four-year grant period will build research capacity and infrastructure, train a diverse STEM workforce, and increase social awareness and acceptability of these technologies among stakeholder populations. The subsequent three-year renewal will achieve long-term sustainability from industrial partnerships and commercialization and bridge major knowledge gaps in utilizing native microbial isolates and nature-inspired minimal genomes to apply aerobic N-fixation in biomanufacturing and agriculture