Engineered biosynthesis of alkyne-tagged polyketides

Area of Science:

• Synthetic biology
• Natural product biosynthesis
• Chemical biology

Background:

• Polyketides are crucial natural products with applications in medicine, industry, and agriculture.
• Tagging polyketides with bioorthogonal functionalities, like terminal alkynes, facilitates their study and manipulation.
• Existing methods often rely on feeding external moieties, which can lead to background noise.

Purpose of the Study:

• To develop a de novo biosynthesis strategy for producing alkyne-tagged polyketides.
• To engineer the JamABC machinery for integration with various downstream polyketide synthases (PKSs).
• To establish guidelines for applying these engineering strategies to other PKS systems.

Main Methods:

• Engineered the JamABC terminal alkyne biosynthetic machinery.
• Integrated JamABC with type III and type I polyketide synthases (PKSs).
• Demonstrated the in situ generation of clickable functionalities on polyketides.

Main Results:

• Successfully produced alkyne-tagged polyketides via de novo biosynthesis.
• Demonstrated successful engineering of both type III and type I PKSs.
• Provided a framework for engineering diverse PKSs for alkyne-tagged metabolite production.

Conclusions:

• De novo biosynthesis of alkyne-tagged polyketides minimizes background interference.
• The engineered JamABC machinery is versatile and applicable to various PKS types.
• This approach offers a powerful tool for generating targeted alkyne-tagged metabolites for chemical and biological applications.