Regeneration of Phytochemicals by Structure‐Driven Organization of Microbial Biosynthetic Steps

Medicinal phytochemicals, such as artemisinin and taxol, have impacted the world, and hypericin might do so if its availability issue could be addressed. Hypericin is the hallmark component of Saint John's wort (Hypericum perforatum L.), an approved depression alleviator documented in the US, E...

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Bibliographic Details
Published in:Angewandte Chemie 2022-02, Vol.134 (8), p.n/a
Main Authors: Wu, Xue Ming, Guan, Qiu Yan, Han, Yun Bin, Wang, Xin Cun, Zhuang, Wen Ying, Tan, Ren Xiang
Format: Article
Language:English
Subjects:
Artemisinin
Biosynthesis
Chemical synthesis
Chemistry
Enzyme catalysis
Hypericin
Indigenous plants
Knowledge acquisition
Microorganisms
Paclitaxel
Phytochemicals
Phytochemistry
Regeneration
Synthetic biology
Viruses
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Summary:Medicinal phytochemicals, such as artemisinin and taxol, have impacted the world, and hypericin might do so if its availability issue could be addressed. Hypericin is the hallmark component of Saint John's wort (Hypericum perforatum L.), an approved depression alleviator documented in the US, European, and British pharmacopoeias with its additional effectiveness against diverse cancers and viruses. However, the academia‐to‐industry transition of hypericin remain hampered by its low in planta abundance, unfeasible bulk chemical synthesis, and unclear biosynthetic mechanism. Here, we present a strategy consisting of the hypericin‐structure‐centered modification and reorganization of microbial biosynthetic steps in the repurposed cells that have been tamed to enable the designed consecutive reactions to afford hypericin (43.1 mg L−1), without acquiring its biosynthetic knowledge in native plants. The study provides a synthetic biology route to hypericin and establishes a platform for biosustainable access to medicinal phytochemicals. To enable access to hypericin, a phytochemical with promising medicinal properties but low natural abundance, a strategy involving structure‐based modification and organization of the microbial biosynthetic steps was developed without knowing its biosynthetic pathway in native plants. The designed consecutive reactions (see scheme) occurred in repurposed cells, thus circumventing the complex plant secondary metabolism.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202114919