Deciphering the biosynthetic pathways of lichen acids.

Area of Science:

• Biochemistry
• Mycology
• Evolutionary Biology

Background:

• Lichen acids, including depsides and depsidones, are polyketide-derived compounds with diverse biological activities.
• The biosynthetic gene clusters (BGCs) governing the production of these lichen acids are largely uncharacterized.
• Understanding these BGCs is crucial for elucidating lichen chemical diversity.

Purpose of the Study:

• To investigate the diversity and evolutionary relationships of polyketide BGCs in lichens.
• To identify the specific BGCs responsible for depside and depsidone biosynthesis.
• To understand the mechanisms driving the structural diversification of lichen acids.

Main Methods:

• Genome mining and phylogenetic analysis of 100 lichen genomes to identify polyketide synthases (PKSs).
• BGC network analysis to assess BGC diversity.
• Heterologous expression of PKS and tailoring enzyme genes to validate BGC function.

Main Results:

• Lecanorales species exhibit the highest PKS diversity.
• pks1 and pks23 were identified as paralogous PKS genes involved in lichen acid biosynthesis.
• Heterologous expression of pks1 yielded 4-O-demethylbarbatic acid, and co-expression with tailoring enzymes produced virensic acid.

Conclusions:

• pks1 and pks23 are paralogous PKSs crucial for medullary depside/depsidone biosynthesis.
• Tailoring enzyme diversity plays a significant role in the structural diversification of lichen acids.
• This research provides key insights into the biosynthesis and evolution of lichen secondary metabolites.