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Title: CHARACTERIZATION OF THE GENE CLUSTER FOR BIOSYNTHESIS OF MACROCYCLIC TRICHOTHECENES IN MYROTHECIUM RORIDUM

Author
item TRAPP, SUSAN - UNIV OF MD, COLLEGE PARK
item Hohn, Thomas
item McCormick, Susan
item JARVIS, BRUCE - UNIV OF MD, COLLEGE PARK

Submitted to: Molecular and General Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/26/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: Macrocyclic trichothecenes are potent fungal toxins produced by both plant pathogenic fungi and fungi implicated as agents of the "sick building syndrome." In order to understand the importance of these toxins in plant disease and as possible environmental contaminants, we have isolated several genes involved in toxin production. Gene mapping experiments indicated these genes are clustered or closely linked. The availability of toxin pathway genes creates opportunities to study toxin function and production.

Technical Abstract: Macrocyclic trichothecenes are toxic sesquiterpenoids that are produced by certain fungi and plants. The unique structural features of macrocyclic trichothecenes result in increased toxicity when compared to other trichothecene structural types. Herein we report the sequences and relative locations of the MRTRI5, MRTRI6, and MRTRI4 genes in the macrocyclic trichothecene pathway of Myrothecium roridum. MRTRI6 encodes a transcription factor required for pathway gene expression, and the predicted MRTRI4 product is a cytochrome P450 monooxygenase responsible for the initial oxygenation step in the pathway. The sizes of MRTRI5 and MRTRI4 sequences show good agreement with their apparent Fusarium pathway counterparts; however, the predicted amino acid sequence of MRTRI6 is almost twice the size of its putative homologue in F. sporotrichioides. MRTRI4 was able to successfully complement a TRI4- mutant in F. sporotrichioides although the resulting trichothecene profile differed from that observed for wild-type strains. Complemented mutants accumulated low levels of T-2 toxin in addition to sambucinol, deoxysambucinol, and the pathway intermediates trichothecene and isotrichodiol. Mapping data indicate that the macrocyclic trichothecene pathway genes in M. roridum are clustered but that the organization and orientation of pathway genes are markedly different from the trichothecene pathway gene cluster found in F. sporotrichioides. These results show that macrocyclic trichothecene pathways are closely related to other trichothecene pathways and that the evolution of fungal natural product pathway gene clusters can involve significant rearrangements.