Clicking into Place: Interfacing Terminal Alkyne Biosynthesis with Polyketide Synthases

Area of Science:

• Synthetic biology
• Biochemistry
• Chemical engineering

Background:

• Engineering polyketide biosynthesis for diverse chemical structures is challenging.
• Modular polyketide synthases (PKS) are key tools in natural product synthesis.
• Terminal alkyne production cassettes offer unique chemical handles.

Purpose of the Study:

• To engineer polyketide biosynthesis for novel chemical structures.
• To interface terminal alkyne production enzymes with modular PKS.
• To introduce bio-orthogonal handles into PKS-derived products.

Main Methods:

• Utilized an established terminal alkyne production biosynthetic cassette.
• Applied docking domain strategies to enzyme engineering.
• Employed site-directed mutagenesis to modify enzyme interactions.
• Interfaced engineered enzymes with modular polyketide synthase (PKS) systems.

Main Results:

• Successfully produced polyketide derivatives with a terminal alkyne group.
• Demonstrated the feasibility of incorporating bio-orthogonal handles into PKS products.
• Enabled the generation of chemically diverse polyketide structures.

Conclusions:

• The engineered system allows for the production of polyketides with a bio-orthogonal handle.
• This approach expands the toolbox for synthetic biology and natural product synthesis.
• Facilitates the creation of novel molecules for various applications.