Genetic organization and function of the aflatoxin B1 biosynthetic genes

Woloshuk, Charles P.; Prieto, Rafael

doi:10.1111/j.1574-6968.1998.tb12907.x

Cited by 85 publications

(48 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, at least two ' minimal versions ' of fungal-type FASs also exist : The specialized secondary metabolism hexanoate synthase (HexAB) complex, which is found in several filamentous fungi and synthesizes the aflatoxin precursor hexanoic acid, is organized into a-and b-chains, but lacks several expansion segments found at the top and the periphery of the FAS particle (Fig. 8 b) (Brown et al 1996 ;Crawford et al 2008 ;Woloshuk & Prieto, 1998). Further reduction is observed in the single-chain type I FAS of mycobacteria, which is involved in the biosynthesis of mycolic acids, major components of the bacterial cell wall.…”

Section: Overall Architecturementioning

confidence: 99%

Structure and function of eukaryotic fatty acid synthases

Maier

Leibundgut

Boehringer

et al. 2010

Quart. Rev. Biophys.

123

127

View full text Add to dashboard Cite

Abstract. In all organisms, fatty acid synthesis is achieved in variations of a common cyclic reaction pathway by stepwise, iterative elongation of precursors with two-carbon extender units. In bacteria, all individual reaction steps are carried out by monofunctional dissociated enzymes, whereas in eukaryotes the fatty acid synthases (FASs) have evolved into large multifunctional enzymes that integrate the whole process of fatty acid synthesis. During the last few years, important advances in understanding the structural and functional organization of eukaryotic FASs have been made through a combination of biochemical, electron microscopic and X-ray crystallographic approaches. They have revealed the strikingly different architectures of the two distinct types of eukaryotic FASs, the fungal and the animal enzyme system. Fungal FAS is a 2Á6 MDa a 6 b 6 heterododecamer with a barrel shape enclosing two large chambers, each containing three sets of active sites separated by a central wheel-like structure. It represents a highly specialized micro-compartment strictly optimized for the production of saturated fatty acids. In contrast, the animal FAS is a 540 kDa X-shaped homodimer with two lateral reaction clefts characterized by a modular domain architecture and large extent of conformational flexibility that appears to contribute to catalytic efficiency.

show abstract

Section: Overall Architecturementioning

confidence: 99%

Structure and function of eukaryotic fatty acid synthases

Maier

Leibundgut

Boehringer

et al. 2010

Quart. Rev. Biophys.

123

127

View full text Add to dashboard Cite

show abstract

“…At least 20 different species of Aspergillus produce the secondary metabolite sterigmatocystin, while only few sythesize the related compound, aflatoxin (180). Both metabolites are derived from a common precursor, norsorolinic acid, which is composed of an anthrachinone-like polyketide to which a hexanoic acid side chain is attached (Fig.…”

Section: Fass Of Secondary Metabolismmentioning

confidence: 99%

Microbial Type I Fatty Acid Synthases (FAS): Major Players in a Network of Cellular FAS Systems

Schweizer

Hofmann

2004

Microbiol Mol Biol Rev

325

286

View full text Add to dashboard Cite

The present review focuses on microbial type I fatty acid synthases (FASs), demonstrating their structural and functional diversity. Depending on their origin and biochemical function, multifunctional type I FAS proteins form dimers or hexamers with characteristic organization of their catalytic domains. A single polypeptide may contain one or more sets of the eight FAS component functions. Alternatively, these functions may split up into two different and mutually complementing subunits. Targeted inactivation of the individual yeast FAS acylation sites allowed us to define their roles during the overall catalytic process. In particular, their pronounced negative cooperativity is presumed to coordinate the FAS initiation and chain elongation reactions. Expression of the unlinked genes, FAS1 and FAS2, is in part constitutive and in part subject to repression by the phospholipid precursors inositol and choline. The interplay of the involved regulatory proteins, Rap1, Reb1, Abf1, Ino2/Ino4, Opi1, Sin3 and TFIIB, has been elucidated in considerable detail. Balanced levels of subunits α and β are ensured by an autoregulatory effect of FAS1 on FAS2 expression and by posttranslational degradation of excess FAS subunits. The functional specificity of type I FAS multienzymes usually requires the presence of multiple FAS systems within the same cell. De novo synthesis of long-chain fatty acids, mitochondrial fatty acid synthesis, acylation of certain secondary metabolites and coenzymes, fatty acid elongation, and the vast diversity of mycobacterial lipids each result from specific FAS activities. The microcompartmentalization of FAS activities in type I multienzymes may thus allow for both the controlled and concerted action of multiple FAS systems within the same cell

show abstract

“…Over 30 years of investigations into the aflatoxin biosynthetic pathway has identified more than 20 enzymes involved. Most of the aflatoxin-related genes are clustered within a 75 kb region of the genome (Trail et al, 1995;Yu et al, 1995;Woloshuk & Prieto, 1998). The aflR gene, which regulates these clustered genes, has been identified in A. flavus, A. parasiticus, A. sojae and A. oryzae.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the aflR gene sequences of strains in Aspergillus section Flavi

2006

View full text Add to dashboard Cite

Aflatoxins are polyketide-derived secondary metabolites produced by Aspergillus parasiticus, Aspergillus flavus, Aspergillus nomius and a few other species. The toxic effects of aflatoxins have adverse consequences for human health and agricultural economics. The aflR gene, a regulatory gene for aflatoxin biosynthesis, encodes a protein containing a zinc-finger DNA-binding motif. Although Aspergillus oryzae and Aspergillus sojae, which are used in fermented foods and in ingredient manufacture, have no record of producing aflatoxin, they have been shown to possess an aflR gene. This study examined 34 strains of Aspergillus section Flavi. The aflR gene of 23 of these strains was successfully amplified and sequenced. No aflR PCR products were found in five A. sojae strains or six strains of A. oryzae. These PCR results suggested that the aflR gene is absent or significantly different in some A. sojae and A. oryzae strains. The sequenced aflR genes from the 23 positive strains had greater than 96·6 % similarity, which was particularly conserved in the zinc-finger DNA-binding domain. The aflR gene of A. sojae has two obvious characteristics: an extra CTCATG sequence fragment and a C to T transition that causes premature termination of AFLR protein synthesis. Differences between A. parasiticus/A. sojae and A. flavus/A. oryzae aflR genes were also identified. Some strains of A. flavus as well as A. flavus var. viridis, A. oryzae var. viridis and A. oryzae var. effuses have an A. oryzae-type aflR gene. For all strains with the A. oryzae-type aflR gene, there was no evidence of aflatoxin production. It is suggested that for safety reasons, the aflR gene could be examined to assess possible aflatoxin production by Aspergillus section Flavi strains.

show abstract

Genetic organization and function of the aflatoxin B1 biosynthetic genes

Cited by 85 publications

References 47 publications

Structure and function of eukaryotic fatty acid synthases

Structure and function of eukaryotic fatty acid synthases

Microbial Type I Fatty Acid Synthases (FAS): Major Players in a Network of Cellular FAS Systems

Comparison of the aflR gene sequences of strains in Aspergillus section Flavi

Contact Info

Product

Resources

About