Type II polyketide synthases: Impact on human health, current knowledge, and future directions

Area of Science:

• Biochemistry
• Natural Product Chemistry
• Molecular Biology

Background:

• Natural products possess significant bioactivity, including antibiotic, antifungal, and anticancer properties.
• Polyketides, synthesized by polyketide synthases (PKSs), represent a major class of these bioactive compounds.
• PKSs share biosynthetic logic with fatty acid synthases but produce greater structural diversity through iterative modifications.

Purpose of the Study:

• To highlight the importance of type II PKS-assembled natural products in human health.
• To elucidate the assembly pathways of these complex molecules.
• To summarize current challenges in PKS research and engineering.

Main Methods:

• Review of existing literature on polyketide biosynthesis and PKS engineering.
• Analysis of the structural diversity and functional roles of polyketides.
• Examination of protein-protein interactions in PKS assembly.

Main Results:

• Polyketide biosynthesis involves distinct steps: initiation, extension, reduction, aromatization/cyclization, and tailoring.
• Engineering PKS, including chimeric constructs, has yielded novel compounds but often with reduced yield and fidelity.
• Protein-protein interactions are critical for efficient and accurate PKS function.

Conclusions:

• Type II PKS-derived natural products are vital for medicine.
• Further research into PKS assembly and protein interactions is necessary for successful engineering of novel therapeutics.
• Overcoming challenges in PKS engineering will unlock new avenues for drug discovery.