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Open Access Research article

Comparative genome sequencing reveals chemotype-specific gene clusters in the toxigenic black mold Stachybotrys

Jeremy Semeiks1*, Dominika Borek2, Zbyszek Otwinowski2 and Nick V Grishin23

Author Affiliations

1 Molecular Biophysics Program and Medical Scientist Training Program, University of Texas Southwestern Medical Center, Dallas, Texas, USA

2 Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA

3 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA

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BMC Genomics 2014, 15:590  doi:10.1186/1471-2164-15-590

Published: 12 July 2014

Abstract

Background

The fungal genus Stachybotrys produces several diverse toxins that affect human health. Its strains comprise two mutually-exclusive toxin chemotypes, one producing satratoxins, which are a subclass of trichothecenes, and the other producing the less-toxic atranones. To determine the genetic basis for chemotype-specific differences in toxin production, the genomes of four Stachybotrys strains were sequenced and assembled de novo. Two of these strains produce atranones and two produce satratoxins.

Results

Comparative analysis of these four 35-Mbp genomes revealed several chemotype-specific gene clusters that are predicted to make secondary metabolites. The largest, which was named the core atranone cluster, encodes 14 proteins that may suffice to produce all observed atranone compounds via reactions that include an unusual Baeyer-Villiger oxidation. Satratoxins are suggested to be made by products of multiple gene clusters that encode 21 proteins in all, including polyketide synthases, acetyltransferases, and other enzymes expected to modify the trichothecene skeleton. One such satratoxin chemotype-specific cluster is adjacent to the core trichothecene cluster, which has diverged from those of other trichothecene producers to contain a unique polyketide synthase.

Conclusions

The results suggest that chemotype-specific gene clusters are likely the genetic basis for the mutually-exclusive toxin chemotypes of Stachybotrys. A unified biochemical model for Stachybotrys toxin production is presented. Overall, the four genomes described here will be useful for ongoing studies of this mold’s diverse toxicity mechanisms.

Keywords:
Stachybotrys; Comparative genomics; Secondary metabolism; Trichothecene biosynthesis; Toxins; Satratoxins; Atranones; Whole-genome sequencing