Polyketide Trimming Shapes Dihydroxynaphthalene‐Melanin and Anthraquinone Pigments

Pigments such as anthraquinones (AQs) and melanins are antioxidants, protectants, or virulence factors. AQs from the entomopathogenic bacterium Photorhabdus laumondii are produced by a modular type II polyketide synthase system. A key enzyme involved in AQ biosynthesis is PlAntI, which catalyzes the hydrolysis of the bicyclic‐intermediate‐loaded acyl carrier protein, polyketide trimming, and assembly of the aromatic AQ scaffold. Here, multiple crystal structures of PlAntI in various conformations and with bound substrate surrogates or inhibitors are reported. Structure‐based mutagenesis and activity assays provide experimental insights into the three sequential reaction steps to yield the natural product AQ‐256. For comparison, a series of ligand‐complex structures of two functionally related hydrolases involved in the biosynthesis of 1,8‐dihydroxynaphthalene‐melanin in pathogenic fungi is determined. These data provide fundamental insights into the mechanism of polyketide trimming that shapes pigments in pro‐ and eukaryotes.

• Publication year

  2024

• Venue

  Advancement of science

• Publication date

  2024-03-16

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1002/advs.202400184PMID 38491909PMCID 11165489
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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