Author
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Ehrlich, Kenneth |
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Submitted to: American Chemical Society Symposium Series
Publication Type: Book / Chapter Publication Acceptance Date: 6/30/2006 Publication Date: 3/1/2007 Citation: Ehrlich, K. 2007. Polyketide Biosynthesis in Fungi. In: Rimando, A.M. and Baerson, S.R., editors. Washington, DC: American Chemical Society. American Chemical Society Symposium Series. 955:68-80. Interpretive Summary: A review of the biology and chemistry of the compounds made by filamentous fungi is given in this manuscript. These compounds are called polyketides because they are made by combining acetic acid and malonic acid by a specialized fatty acid producing enzyme called a polyketide synthase. Different types of synthases produce the starting material for different compounds. The fungi, Aspergillus flavus and A. oryzae, have about 30 different polyketide synthases. One of them is responsible for making aflatoxin, a poisonous and cancer-causing compound made only by a few Aspergillus species. We present a comprehensive up-to-date discussion of the many enzymes needed for aflatoxin production by Aspergillus. Some of these enzymes are only made by these and very similar Aspergillus species. After the backbone for aflatoxin is made by the polyketide synthase enzymes, many other enzymes are involved in the decoration of this polyketide. Most of the enzymes are oxidative enzymes. The genes that make these enzymes are grouped in a cluster. The cluster organization is important for the ability of the fungi to produce aflatoxins. I also discuss a model for how and why the ability for aflatoxin production may have evolved. The review may be of interest to scientists and researchers. Technical Abstract: Elaborate arrays of polyketide metabolites are produced by filamentous fungi. Polyketides are produced by iterative condensation of malonylCoA by a specialized type of fatty acid synthase that often lacks some or all of the reducing domains normally found in such enzymes. Fungal polyketide synthases (PKSs) have a single polypeptide chain with multiple independently acting catalytic domains. The structure of the resulting polyketide depends on the type of coenzymeA (CoA) starter unit upon which the polyketide is built, whether or not reducing domains are present in the PKS, how the polyketide chain is terminated and the types of oxidative enzymes that perform subsequent modifications. A contiguous set of genes encoding the regulatory and metabolic enzymes is usually required for the biosynthesis of polyketides. The most extensively studied biosynthetic gene cluster is for the carcinogenic mycotoxin, aflatoxin (AF). AF is formed from a hexanoyl CoA precursor by PKS-catalyzed condensation of seven malonyl CoA units and a series of oxidative steps performed by six cytochrome P450 monooxygenases, nine oxidoreductases and three non-oxidative enzymes. Since there is no evidence that these enzymes are produced sequentially, the subsequent oxidations of the polyketide precursor are most likely dictated by the chemical susceptibility of the individual precursor metabolites formed at each step. |
