scholarly journals Diterpene Biosynthesis in Catenulispora acidiphila : On the Mechanism of Catenul‐14‐en‐6‐ol Synthase

Author(s):  
Geng Li ◽  
Yue‐Wei Guo ◽  
Jeroen S. Dickschat
2009 ◽  
Vol 75 (23) ◽  
pp. 7469-7481 ◽  
Author(s):  
Matthew J. Nicholson ◽  
Albert Koulman ◽  
Brendon J. Monahan ◽  
Beth L. Pritchard ◽  
Gary A. Payne ◽  
...  

ABSTRACT Aflatrem is a potent tremorgenic toxin produced by the soil fungus Aspergillus flavus, and a member of a structurally diverse group of fungal secondary metabolites known as indole-diterpenes. Gene clusters for indole-diterpene biosynthesis have recently been described in several species of filamentous fungi. A search of Aspergillus complete genome sequence data identified putative aflatrem gene clusters in the genomes of A. flavus and Aspergillus oryzae. In both species the genes for aflatrem biosynthesis cluster at two discrete loci; the first, ATM1, is telomere proximal on chromosome 5 and contains a cluster of three genes, atmG, atmC, and atmM, and the second, ATM2, is telomere distal on chromosome 7 and contains five genes, atmD, atmQ, atmB, atmA, and atmP. Reverse transcriptase PCR in A. flavus demonstrated that aflatrem biosynthesis transcript levels increased with the onset of aflatrem production. Transfer of atmP and atmQ into Penicillium paxilli paxP and paxQ deletion mutants, known to accumulate paxilline intermediates paspaline and 13-desoxypaxilline, respectively, showed that AtmP is a functional homolog of PaxP and that AtmQ utilizes 13-desoxypaxilline as a substrate to synthesize aflatrem pathway-specific intermediates, paspalicine and paspalinine. We propose a scheme for aflatrem biosynthesis in A. flavus based on these reconstitution experiments in P. paxilli and identification of putative intermediates in wild-type cultures of A. flavus.


2019 ◽  
Vol 58 (45) ◽  
pp. 15964-15976 ◽  
Author(s):  
Jeroen S. Dickschat

1992 ◽  
Vol 99 (3) ◽  
pp. 1169-1178 ◽  
Author(s):  
Yue-Ying Ren ◽  
Charles A. West

2004 ◽  
Vol 70 (11) ◽  
pp. 6875-6883 ◽  
Author(s):  
Shuguang Zhang ◽  
Brendon J. Monahan ◽  
Jan S. Tkacz ◽  
Barry Scott

ABSTRACT Aflatrem is a potent tremorgenic mycotoxin produced by the soil fungus Aspergillus flavus and is a member of a large structurally diverse group of secondary metabolites known as indole-diterpenes. By using degenerate primers for conserved domains of fungal geranylgeranyl diphosphate synthases, we cloned two genes, atmG and ggsA (an apparent pseudogene), from A. flavus. Adjacent to atmG are two other genes, atmC and atmM. These three genes have 64 to 70% amino acid sequence similarity and conserved synteny with a cluster of orthologous genes, paxG, paxC, and paxM, from Penicillium paxilli which are required for indole-diterpene biosynthesis. atmG, atmC, and atmM are coordinately expressed, with transcript levels dramatically increasing at the onset of aflatrem biosynthesis. A genomic copy of atmM can complement a paxM deletion mutant of P. paxilli, demonstrating that atmM is a functional homolog of paxM. Thus, atmG, atmC, and atmM are necessary, but not sufficient, for aflatrem biosynthesis by A. flavus. This provides the first genetic evidence for the biosynthetic pathway of aflatrem in A. flavus.


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