Hexanoate Synthase, a Specialized Type I Fatty Acid Synthase in Aflatoxin B1 Biosynthesis

Hitchman, Timothy S.

doi:10.1006/bioo.2001.1216

Cited by 47 publications

(32 citation statements)

References 30 publications

(29 reference statements)

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“…1 and Supplementary Table 1). A third promising KS mutation was identified in sequence alignments with FASs of reported C 6 -FA producers, such as Aspergillus nidulans , Aspergillus parasiticus and Aspergillus flavus 2728. The residue F1279 is protruding into the KS binding channel from the opposite side of G1250S-M1251W (Fig.…”

Section: Resultsmentioning

confidence: 99%

Engineering fungal de novo fatty acid synthesis for short chain fatty acid production

et al. 2017

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Fatty acids (FAs) are considered strategically important platform compounds that can be accessed by sustainable microbial approaches. Here we report the reprogramming of chain-length control of Saccharomyces cerevisiae fatty acid synthase (FAS). Aiming for short-chain FAs (SCFAs) producing baker's yeast, we perform a highly rational and minimally invasive protein engineering approach that leaves the molecular mechanisms of FASs unchanged. Finally, we identify five mutations that can turn baker's yeast into a SCFA producing system. Without any further pathway engineering, we achieve yields in extracellular concentrations of SCFAs, mainly hexanoic acid (C6-FA) and octanoic acid (C8-FA), of 464 mg l−1 in total. Furthermore, we succeed in the specific production of C6- or C8-FA in extracellular concentrations of 72 and 245 mg l−1, respectively. The presented technology is applicable far beyond baker's yeast, and can be plugged into essentially all currently available FA overproducing microorganisms.

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Section: Resultsmentioning

confidence: 99%

Engineering fungal de novo fatty acid synthesis for short chain fatty acid production

et al. 2017

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“…For example, the biosynthesis of the fungal polyketide aflatoxin in select Aspergillus species 39-41 involves an NR-PKS, PksA, 42 in a FAS-PKS hybrid complex 43, 44 . The NR-PKS accepts a C 6 -fatty acid starter 45-47 from a dedicated fungal FAS 31, 48, 49 , further homologates seven malonyl-CoA extender units and controls specific folding and cyclization to produce the aflatoxin B 1 ( 10 ) precursor, norsolorinic acid anthrone ( 8 ). The anthrone is oxidized to the anthraquinone norsolorinic acid ( 9 ) by an anthrone oxidase 50 .…”

Section: Biochemical Basis For Starter-unit Selectionmentioning

confidence: 99%

New insights into the formation of fungal aromatic polyketides

2010

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Fungal aromatic polyketides constitute a large family of bioactive natural products and are synthesized by the non-reducing group of iterative polyketide synthases (NR-PKSs). Their diverse structures arise from selective enzymatic modifications of reactive enzyme-bound poly-β-keto intermediates. How iterative PKSs control starter unit selection, polyketide chain initiation and elongation, intermediate folding and cyclization, selective redox or modification reactions during assembly, and product release are central mechanistic questions underlying iterative catalysis. This review highlights recent insights into these questions, with a particular focus on the biosynthetic programming of fungal aromatic polyketides, and draws comparisons to the allied biosynthetic processes in bacteria.

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“…However, the relative contribution of each PKS to T-toxin synthesis is unknown. As noted above, T-toxin lacks the ester group formed in lovastatin through the concatenation of the two polyketide chains, and the putative PKS1 and PKS2 gene products appear to be joined by a carbon-carbon bond, reminiscent of the mechanism of aflatoxin synthesis (Hitchman et al 2001;Yabe and Nakajima 2004). Synthesis of the aflatoxin backbone requires the interaction of a fatty acid synthetase (FAS) and a PKS, two proteins with the same domain structure, encoded by members of the same gene superfamily (Hopwood 1997).…”

Section: Figmentioning

confidence: 99%

“…Synthesis of the aflatoxin backbone requires the interaction of a fatty acid synthetase (FAS) and a PKS, two proteins with the same domain structure, encoded by members of the same gene superfamily (Hopwood 1997). The FAS synthesizes a C 6 starter unit for the PKS (Hitchman et al 2001). PKS1 and PKS2 could interact in a similar way.…”

Section: Figmentioning

confidence: 99%

Two Polyketide Synthase-Encoding Genes Are Required for Biosynthesis of the Polyketide Virulence Factor, T-toxin, by Cochliobolus heterostrophus

Baker

Kroken²,

Inderbitzin³

et al. 2006

MPMI

128

101

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Cochliobolus heterostrophus race T, causal agent of southern corn leaf blight, requires T-toxin (a family of C35 to C49 polyketides) for high virulence on T-cytoplasm maize. Production of T-toxin is controlled by two unlinked loci, Tox1A and Tox1B, carried on 1.2 Mb of DNA not found in race O, a mildly virulent form of the fungus that does not produce T-toxin, or in any other Cochliobolus spp. or closely related fungus. PKS1, a polyketide synthase (PKS)-encoding gene at Tox1A, and DEC1, a decarboxylase-encoding gene at Tox1B, are necessary for T-toxin production. Although there is evidence that additional genes are required for T-toxin production, efforts to clone them have been frustrated because the genes are located in highly repeated, A+T-rich DNA. To overcome this difficulty, ligation specificity-based expression analysis display (LEAD), a comparative amplified fragment length polymorphism/gel fractionation/capillary sequencing procedure, was applied to cDNAs from a near-isogenic pair of race T (Tox1+) and race O (Tox1-) strains. This led to discovery of PKS2, a second PKS-encoding gene that maps at Tox1A and is required for both T-toxin biosynthesis and high virulence to maize. Thus, the carbon chain of each T-toxin family member likely is assembled by action of two PKSs, which produce two polyketides, one of which may act as the starter unit for biosynthesis of the mature T-toxin molecule.

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Hexanoate Synthase, a Specialized Type I Fatty Acid Synthase in Aflatoxin B1 Biosynthesis

Cited by 47 publications

References 30 publications

Engineering fungal de novo fatty acid synthesis for short chain fatty acid production

Engineering fungal de novo fatty acid synthesis for short chain fatty acid production

New insights into the formation of fungal aromatic polyketides

Two Polyketide Synthase-Encoding Genes Are Required for Biosynthesis of the Polyketide Virulence Factor, T-toxin, by Cochliobolus heterostrophus

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