摘要
Scutellarin related drugs have superior therapeutic effects on cerebrovascular and cardiovascular diseases.Here,an optimal biosynthetic pathway for scutellarin was constructed in Yarrowia lipolytica platform due to its excellent metabolic potential.By integrating multi-copies of core genes from different species,the production of scutellarin was increased from 15.11 mg/L to 94.79 mg/L and the ratio of scutellarin to the main by-product was improved about 110-fold in flask condition.Finally,the production of scutellarin was improved 23-fold and reached to 346 mg/L in fed-batch bioreactor,which was the highest reported titer for de novo production of scutellarin in microbes.Our results represent a solid basis for further production of natural products on unconventional yeasts and have a potential of industrial implementation.
基金
funding from the Major Science and Technique Programs in Yunnan Province(No.2019ZF011-1)
the National Natural Science Foundation of China(No.81960689)
the National Key R&D Program of China(2020YFC1316400)
the Project of Young and Middle-Aged Talent of Yunnan Province(No.2019HB019)
Science and Technology Innovation team of Yunnan(No.202105AE160011)
Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(No.TSBICIP-KJGG-002-02)
the Tianjin Science Fund for Distinguished Young Scholars(No.18JCJQJC48300).