Improved production of human hemoglobin in yeast by engineering hemoglobin degradation

With the increasing demand for blood transfusions, production of human hemoglobin (Hb) from sustainable sources is increasingly studied. Microbial an attractive option, as it may provide a cheap, safe, and reliable source this protein. To increase by yeast Saccharomyces cerevisiae, degradation Hb was reduced through several approaches. The deletion genes HMX1 (encoding heme oxygenase), VPS10 receptor vacuolar proteases), PEP4 proteinase A), ROX1 heme-dependent repressor hypoxic genes) overexpression HEM3 porphobilinogen deaminase) AHSP alpha-hemoglobin-stabilizing protein) — these changes improved production. validated bilirubin biosensor. During glucose fermentation, engineered strains produced 18% intracellular relative to total protein, which highest reported in yeast. This increased accompanied with oxygen consumption rate glycerol yield, (we speculate) yeast's response rebalance its NADH levels under conditions limitation protein-production.