Synthesis of Poly (β-L-malic Acid) by the Optimization of Inorganic Nitrogen Complexing with Growth Factors Using Aureobasidium pullulans CGMCC3337

Abstract

Poly (β-L-malic acid) (PMLA) can be used as a prodrug or used for drug delivery system, and it has attracted industrial interest. In previous studies, we could obtain 38 g/L PMLA with 10 g/L yeast extract as a nitrogen source, but the complex broth component made it difficult to the downstream process. To decrease the pressure in the extraction process, we used inorganic nitrogen resources and growth factors to replace yeast extract. Response surface methodology (RSM) was applied to optimize the fermentation medium formulation to improve the production of poly (β-L-malic acid) (PMLA) with Aureobasidium pullulans CGMCC3337. It was confirmed that ammonium nitrate 2.06 g/L, adenine 0.02 g/L, cytosine 0.012 g/L aspartate (Asp) 0.42 g/L, histidine(His) 0.6 g/L, leucine(Leu) 0.4 g/L, and threonine(Thr) 0.28 g/L could replace the yeast extract in PMLA production. The model developed based on RSM successfully predicted PMLA productivity (R ² = 0.9697). With the optimum medium established, 37.62 g/L PMLA was accumulated in the fermentation broth, and the impurities in the fermentation broth was reduced apparently.