Evolving biosynthetic tangos negotiate mechanistic landscapes

Area of Science:

• Biochemistry
• Evolutionary Biology
• Enzymology

Background:

• Polyketide synthases (PKS) and terpene cyclases (TC) are crucial enzyme families involved in synthesizing diverse natural products.
• These enzymes catalyze complex cyclization reactions, but their mechanistic adaptations and evolutionary relationships are not fully understood.

Purpose of the Study:

• To investigate the convergent evolutionary strategies employed by PKS and TC enzyme families.
• To elucidate how substrate chemistry influences the mechanistic adaptation of these enzymes.
• To understand the interplay between enzymes and substrates in determining reaction outcomes.

Main Methods:

• Comparative analysis of PKS and TC enzyme families.
• Investigating the role of substrate chemistry in enzyme mechanism.
• Exploring evolutionary pathways of cyclization reactions.

Main Results:

• Enzyme adaptation in PKS and TC is significantly dependent on the chemistry of their oligomeric substrates.
• A convergent evolutionary strategy shapes cyclization in these distinct enzyme families.
• Enzyme-substrate interactions form a 'rhythmic tango,' where both dictate product outcome through negotiated chemical reactivities.

Conclusions:

• The study reveals a shared evolutionary strategy for cyclization in PKS and TC, driven by substrate chemistry.
• Evolutionary adaptation in these enzyme families is a collaborative process between the enzyme and its substrate.
• Understanding these 'rhythmic tangos' provides insights into the evolution of complex chemical synthesis in nature.