As an important component of hemoglobin, heme is a porphyrin derivative which involved in the transport and combination of oxygen and other metabolic pathways.In this study, a Pichia pastoris strain with high heme productivity was used as the starting strain. The fermentation conditions were optimized to enhance the heme production in a 5 L fermenter, from the factors of pH, ferrous ion concentration, temperature, and dissolved oxygen level.Then the growth kinetics and production kinetics of the optimal fermentation condition were simulated.It was determined that controlling pH at 4 was the most favorable for heme production.The daily addition of 2 mL of FeSO4·7H2O solution (100 mg/L) adequately could satisfy the ferrous ion requirements for heme production, resulting in a heme production of 160.1 mg/L.The strategy of reducing temperature to enhance expression levels employed in the methanol supplementation fermentation process did not obtain the anticipated outcome in the glycerol supplementation fermentation process.Conversely, it resulted in a decline in heme production.In addition, by comparing different dissolved oxygen levels, it was found that increasing dissolved oxygen had no obvious effect on the accumulation of heme, but could effectively improve the cell growth.Finally, result of kinetic model fitting presented that the accumulation of heme was coupled with the cell growth.The obtained results could serve as references for the industrial fermentation production of heme.
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