Engineered Microbes for Producing Anticholinergics.

Area of Science:

• Biotechnology
• Metabolic Engineering
• Pharmacology

Background:

• Tropane alkaloids (TAs), including hyoscyamine and scopolamine, are acetylcholine receptor antagonists used clinically as parasympatholytics.
• Current TA production relies on intensive agriculture of Duboisia shrubs, facing challenges from climate and pandemics.
• The complex structures of TAs hinder efficient industrial chemical synthesis.

Purpose of the Study:

• To develop an alternative, sustainable production method for tropane alkaloids.
• To engineer a microbial cell factory for de novo synthesis of hyoscyamine and scopolamine.

Main Methods:

• Utilized principles from microbial production of artemisinin.
• Engineered a yeast cell factory for de novo TA biosynthesis.
• Leveraged metabolic engineering strategies for compound accumulation.

Main Results:

• Successfully established a yeast cell factory capable of synthesizing hyoscyamine and scopolamine.
• Demonstrated the feasibility of microbial de novo synthesis for complex TAs.
• Paved the way for a reliable and scalable alternative to agricultural production.

Conclusions:

• Microbial production offers a promising solution to the supply challenges of tropane alkaloids.
• Yeast cell factories represent a viable platform for producing valuable plant-derived pharmaceuticals.
• This approach enhances supply chain stability and reduces reliance on traditional agriculture.