A gene cluster encoding resistomycin biosynthesis in Streptomyces resistomycificus; exploring polyketide cyclization...

Area of Science:

• Microbiology
• Molecular Biology
• Natural Product Chemistry

Background:

• Resistomycin is a unique discoid polyketide from Streptomyces resistomycificus with pharmacological relevance.
• Bacterial aromatic polyketides are typically linear or angular, unlike resistomycin's distinct structure.

Purpose of the Study:

• To identify the gene cluster responsible for resistomycin biosynthesis.
• To elucidate the molecular basis of resistomycin's unique discoid structure and cyclization.

Main Methods:

• Heterologous expression of a cosmid library from Streptomyces resistomycificus.
• Screening for metabolite fluorescence to identify positive clones.
• Bioinformatic analysis of the identified gene cluster (rem).

Main Results:

• The complete resistomycin (rem) gene cluster was identified.
• The cluster contains unusual type II polyketide synthase (PKS) components, including a putative malonyl-CoA:ACP transacylase (MCAT) with homology to modular PKS AT domains.
• Novel insights into the cyclization mechanism producing the discoid polyketide structure were obtained.

Conclusions:

• The identified rem gene cluster provides a platform for understanding resistomycin biosynthesis.
• The unique features of the PKS machinery offer new perspectives on polyketide diversity and engineering.
• This study illuminates the molecular basis for the formation of a rare discoid polyketide structure.