Lesson plan

Arylomycin

The arylomycins are a class of antibiotics initially isolated from a soil sample obtained in Cape Coast, Ghana. In this initial isolation, two families of closely related arylomycins, A and B, were identified. The family of glycosylated arylomycin C lipopeptides were subsequently isolated from a Streptomyces culture in a screen for inhibitors of bacterial signal peptidase. The initially isolated arylomycins have a limited spectrum of activity against Gram-positive bacteria, including Staphylococcus aureus and Streptococcus pneumoniae. The only activity against Gram-negative bacteria was seen in strains with a compromised outer membrane. Following their initial identification and characterization, co-crystal structures with the E. coli signal peptidase were determined and showed that the core of the arylomycins binds to the signal peptidase with the alanine residue in the macrocyclic ring taking the place of the P3 alanine residue in the signal peptidase Ala-X-Ala recognition motif. Additionally, the C terminus of the arylomycins is seen to be within hydrogen bonding distance of the serine/lysine catalytic dyad.…

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Article summary

The arylomycins are a class of antibiotics initially isolated from a soil sample obtained in Cape Coast, Ghana. In this initial isolation, two families of closely related arylomycins, A and B, were identified. The family of glycosylated arylomycin C lipopeptides were subsequently isolated from a Streptomyces culture in a screen for inhibitors of bacterial signal peptidase. The initially isolated arylomycins have a limited spectrum of activity against Gram-positive bacteria, including Staphylococcus aureus and Streptococcus pneumoniae. The only activity against Gram-negative bacteria was seen in strains with a compromised outer membrane. Following their initial identification and characterization, co-crystal structures with the E. coli signal peptidase were determined and showed that the core of the arylomycins binds to the signal peptidase with the alanine residue in the macrocyclic ring taking the place of the P3 alanine residue in the signal peptidase Ala-X-Ala recognition motif. Additionally, the C terminus of the arylomycins is seen to be within hydrogen bonding distance of the serine/lysine catalytic dyad.…

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Discussion questions

  1. Summarise the article in your own words. Which single claim would you verify first, and why?
  2. Which claim in this article is most likely to be revised as the sources update? How would you check its current status?
  3. If two sources disagreed about one of these facts, what would you need in order to trust one over the other?

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