A phylogenetic and evolutionary analysis of antimycin biosynthesis

Area of Science:

• Microbiology and Genomics
• Natural Product Biosynthesis
• Drug Discovery

Background:

• Actinobacteria, including Streptomyces, are prolific sources of antibiotics.
• Antimycin inhibits mitochondrial respiration and anti-apoptotic proteins, relevant for cancer therapy.
• Genomic data offers insights into natural product biosynthetic gene clusters (BGCs).

Purpose of the Study:

• To identify and classify antimycin BGCs in Actinobacteria genomes.
• To analyze the biogeographical distribution and phylogenetic relationships of antimycin BGCs.
• To infer the evolutionary history of antimycin biosynthesis.

Main Methods:

• Bioinformatic analysis of 73 putative antimycin BGCs from public Actinobacteria genomes.
• Classification of BGCs based on the presence/absence of key genes: antP (kynureninase) and antQ (phosphopantetheinyl transferase, PPTase).
• Evaluation of geographical distribution and phylogenetic analysis of BGCs and producers.

Main Results:

• Identified 73 antimycin BGCs, classified into L-form (antP and antQ present), S-form (neither present), IQ-form (only antP absent), and IP-form (only antQ absent).
• Antimycin BGCs are globally distributed across five continents, frequently associated with plants and higher organisms.
• Two distinct phylogenetic clades of producers and BGCs were identified, separating S-form from L- and I-forms.

Conclusions:

• The study provides a comprehensive catalog and classification of antimycin BGCs.
• Evolutionary analysis suggests an ancestral L-form BGC that diversified through vertical transmission.
• Findings contribute to understanding antibiotic natural product diversity and evolution in Actinobacteria.