4.7 Article

Aspergillus oryzae Biosynthetic Platform for de Novo Iridoid Production

期刊

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 69, 期 8, 页码 2501-2511

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.0c06563

关键词

iridoid; nepetalactol; Aspergillus oryzae; biosynthetic platform; metabolic engineering

资金

  1. National Natural Science Foundation of China [31871780]
  2. Fundamental Research Funds for the Central Universities [2662018PY059, 2019BC014]

向作者/读者索取更多资源

The study successfully developed a high nepetalactol-producing Aspergillus oryzae platform strain by co-expressing 5 nepetalactol biosynthetic genes in a high isopentenyl pyrophosphate (IPP) producing strain, achieving the biosynthesis of nepetalactol and improving IPP supply while suppressing the byproduct citronellol formation. The engineered strain achieved the highest titer of nepetalactol after optimization of the carbon source, representing the highest reported titer in microbial cells.
The iridoids and their derivatives monoterpene indole alkaloids (MIAs) are two broad classes of plant-derived natural products with valuable pharmaceutical properties. However, the poor source limited their application. Nepetalactol, a common iridoid scaffold of MIAs, was heterologously produced in Saccharomyces cerevisiae. Although the optimization of nepetalactol production in S. cerevisiae was achieved by metabolic engineering, the inherent metabolic constraints impose a restriction on the production. Herein, we developed a high nepetalactol-producing Aspergillus oryzae platform strain. First, the co-expression of 5 nepetalactol biosynthetic genes, in a high isopentenyl pyrophosphate (IPP)-producing strain A. oryzae AK2, succeeded in the biosynthesis of nepetalactol. Second, the improvement of the IPP supply and the suppression of the byproduct citronellol formation were simultaneously achieved. Finally, the highest titer of nepetalactol of 7.2 mg/L was obtained with the engineered strain, after the optimization of the carbon source. To the best of our knowledge, this is the highest reported titer of nepetalactol in microbial cells. The developed A oryzae strain represents an attractive biosynthetic platform host for the de novo production of iridoids and MIAs.

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