Anthracycline Biosynthesis in <i>Streptomyces galilaeus</i>

Fujii, Isao; Ebizuka, Yutaka

doi:10.1021/cr960019d

Cited by 48 publications

(26 citation statements)

References 64 publications

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“…On this basis, a protein radical mechanism in which the enzyme extracts a proton and electron from the substrate to yield a phenolic radical form of the polyketide substrate, which then reacts with molecular oxygen, has been proposed (29,30). This leaves a radical enzyme species.…”

Section: Discussionmentioning

confidence: 99%

Structural and Biochemical Evidence for an Enzymatic Quinone Redox Cycle in Escherichia coli

Adams¹,

Jia

2005

Journal of Biological Chemistry

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Naturally synthesized quinones perform a variety of important cellular functions. Escherichia coli produce both ubiquinone and menaquinone, which are involved in electron transport. However, semiquinone intermediates produced during the one-electron reduction of these compounds, as well as through auto-oxidation of the hydroxyquinone product, generate reactive oxygen species that stress the cell. Here, we present the crystal structure of YgiN, a protein of hitherto unknown function. The three-dimensional fold of YgiN is similar to that of ActVA-Orf6 monooxygenase, which acts on hydroxyquinone substrates. YgiN shares a promoter with "modulator of drug activity B," a protein with activity similar to that of mammalian DT-diaphorase capable of reducing mendione. YgiN was able to reoxidize menadiol, the product of the "modulator of drug activity B" (MdaB) enzymatic reaction. We therefore refer to YgiN as quinol monooxygenase. Modulator of drug activity B is reported to be involved in the protection of cells from reactive oxygen species formed during single electron oxidation and reduction reactions. The enzymatic activities, together with the structural characterization of YgiN, lend evidence to the possible existence of a novel quinone redox cycle in E. coli.

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Section: Discussionmentioning

confidence: 99%

Structural and Biochemical Evidence for an Enzymatic Quinone Redox Cycle in Escherichia coli

Adams¹,

Jia

2005

Journal of Biological Chemistry

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“…8). While the conversion of a linear heptaketide into the bicyclo [7.3.0]enediyne core must proceed in multiple steps, involving unprecedented reaction mechanisms, polyketide biosynthesis could be readily tested by attempting to clone the putative PKS genes for 3 according to the various methods developed for aromatic polyketide (82,84), macrolide (52), and polyene (57) biosynthesis in streptomycetes.…”

Section: Figmentioning

confidence: 99%

“…Dynemicin is extremely cytotoxic and causes both single-and double-stranded DNA cuts. In addition, due to common structural elements, the extensive progress in anthracycline antibiotic biosynthesis should be beneficial in understanding the biosynthesis of 6 (82)(83)(84).…”

Section: -Membered Nonchromoprotein Enediynesmentioning

confidence: 99%

Enediyne Biosynthesis and Self-Resistance: A Progress Report

Thorson

Shen

Whitwam

et al. 1999

Bioorganic Chemistry

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“…They act principally by inhibiting topoisomerase II (1). Complete or partial biosynthetic clusters for daunorubicin (2), doxorubicin (3), nogalamycin (4), aclacinomycin (5,6), and rhodomycin (7) have been cloned and used for combinatorial biosynthesis of new anthracyclines (4, 8 -10). The success of combinatorial biosynthesis rests on the ability of individual enzymes to accept non-natural substrates.…”

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confidence: 99%

Aclacinomycin 10-Hydroxylase Is a Novel Substrate-assisted Hydroxylase Requiring S-Adenosyl-l-methionine as Cofactor

Jansson

Koskiniemi

Erola

et al. 2005

Journal of Biological Chemistry

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Aclacinomycin 10-hydroxylase is a methyltransferase homologue that catalyzes a S-adenosyl-L-methionine (AdoMet)-dependent hydroxylation of the C-10 carbon atom of 15-demethoxy-⑀-rhodomycin, a step in the biosynthesis of the polyketide antibiotic ␤-rhodomycin. SAdenosyl-L-homocysteine is an inhibitor of the enzyme, whereas the AdoMet analogue sinefungin can act as cofactor, indicating that a positive charge is required for catalysis.18 O 2 experiments show that the hydroxyl group is derived from molecular oxygen.

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Anthracycline Biosynthesis in Streptomyces galilaeus

Cited by 48 publications

References 64 publications

Structural and Biochemical Evidence for an Enzymatic Quinone Redox Cycle in Escherichia coli

Structural and Biochemical Evidence for an Enzymatic Quinone Redox Cycle in Escherichia coli

Enediyne Biosynthesis and Self-Resistance: A Progress Report

Aclacinomycin 10-Hydroxylase Is a Novel Substrate-assisted Hydroxylase Requiring S-Adenosyl-l-methionine as Cofactor

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