Aureothin Explained

Aureothin is a natural product of a cytotoxic shikimate-polyketide antibiotic with the molecular formula C₂₂H₂₃NO₆.^{[1] [2]} Aureothin is produced by the bacterium Streptomyces thioluteus^[3] that illustrates antitumor, antifungal, and insecticidal activities and the new aureothin derivatives can be antifungal and antiproliferative.^[1] In addition, aureothin, a nitro compound from Streptomyces thioluteus, was indicated to have pesticidal activity against the bean weevil^[4] by interfering with mitochondrial respiratory complex II.^[5]

Biosynthesis

Regarding the biosynthesis of aureothin, the biosynthetic pathway would be begun with chorismic acid. P-nitrobenzoate is derived from p-aminobenzoate by an N-oxygenase, which is encoded by aurF.^[6] The aurF is one of the aureothin biosynthetic enzymes and it is referred to as a nonheme diiron oxygenase that is responsible for converting p-aminobenzoate to p-nitrobenzoate.^[7] Moreover, the aurF catalyzes a reaction of a complete six-electron oxidation utilizing two equivalents of dioxygen and two exogenous electrons in order to convert p-aminobenzoate to p-nitrobenzoate. Then, three type I Polyketide Synthases (PKSs), which is encoded by aurA, aurB, and aurC, generates the a polyketide chain using p-nitrobenzoate as a starter unit^[8] for the biosynthesis of aureothin. At this point, the repetition that one molecule catalyzes two successive cycles of chain extension would occur in the reaction of the type I Polyketide Synthase (PKS).^[9] In particular, the two consecutive cycles containing four times of methylmalonyl-CoA and one time of malonyl-CoA occur during the type I Polyketide Synthase (PKS). After O-methylation is activated by a methyltransferase, which is encoded by aurI, the tetrahydrofuran ring formation is produced by a monooxygenase that is encoded by aurH. Therefore, the final product, aureothin, is produced as a result of the monooxygenase encoded by aurH.^[10]

Further reading

• Book: Natural Product Biosynthesis by Microorganisms and Plants Part C . 31 December 2012 . Academic Press . 978-0-12-404617-7 . 216 . en.
• Book: Strategies and Tactics in Organic Synthesis . 4 October 2016 . Elsevier . 978-0-08-100762-4 . 120 . en.

Notes and References

1. Book: Issues in Chemistry and General Chemical Research . 2011 . 9 January 2012 . ScholarlyEditions . 978-1-4649-6334-6 . 442.
2. He . Jing . Hertweck . Christian . Biosynthetic Origin of the Rare Nitroaryl Moiety of the Polyketide Antibiotic Aureothin: Involvement of an Unprecedented N-Oxygenase . Journal of the American Chemical Society . 1 March 2004 . 126 . 12 . 3694–3695 . 10.1021/ja039328t. 15038705 .
3. Hirata . Yoshimasa . Nakata . Hisao . Yamada . Kiyoyuki . Okuhara . Kunio . Naito . Takayuki . The structure of aureothin, a nitro compound obtained from Streptomyces thioluteus . Tetrahedron . January 1961 . 14 . 3–4 . 252–274 . 10.1016/S0040-4020(01)92175-1.
4. Oishi . H. . Hosokawa . T. . Okutomi . T. . Suzuki . K. . Pesticidal Activity of Aureothin . Agricultural and Biological Chemistry . 1969 . 33 . 12 . 1790–1791. 10.1080/00021369.1969.10859541 .
5. Friedrich . T . Van Heek . P . Leif . H . Ohnishi . T . Forche . E . Kunze . B . Jansen . R . Trowitzsch-Kienast . W . Hofle . G . Reichenhach . H . Two binding sites of inhibitors in NADH: ubiquinone oxidoreductase (complex I). Relationship of one site with the ubiquinone-binding site of bacterial glucose:ubiquinone oxidoreductase . Eur. J. Biochem. . 1994 . 219 . 1 . 691–698. 10.1111/j.1432-1033.1994.tb19985.x . 8307034 . free .
6. He . Jing . Hertweck . Christian . Biosynthetic Origin of the Rare Nitroaryl Moiety of the Polyketide Antibiotic Aureothin: Involvement of an Unprecedented N-Oxygenase . J. Am. Chem. Soc. . 2004 . 126 . 12 . 3694–3695. 10.1021/ja039328t . 15038705 .
7. Tsunematsu . Yuta . Hirayama . Yuichiro . Masuya . Takahiro . Watanabe . Kenji . Oxidative Modification Enzymes in Polyketide Biosynthetic Pathways . Comprehensive Natural Products III (Third Edition) . 2020 . 1 . 479–505. 10.1016/B978-0-12-409547-2.14637-2 . 9780081026915 . 201202729 .
8. He . Jing . Hertweck . Christian . Functional Analysis of the Aureothin Iterative Type I Polyketide Synthase . ChemBioChem . 2005 . 6 . 5 . 908–912. 10.1002/cbic.200400333 . 15812854 . 27585538 .
9. He . Jing . Hertweck . Christian . Biosynthetic Origin of the Rare Nitroaryl Moiety of the Polyketide Antibiotic Aureothin: Involvement of an Unprecedented N-Oxygenase . J. Am. Chem. Soc. . 2004 . 126 . 12 . 3694–3695. 10.1021/ja039328t . 15038705 .
10. Sugimoto . Yuki . Ishida . Keishi . Traitcheva . Nelly . Busch . Benjamin . Dahse . Hans-Martin . Hertweck . Christian . Freedom and Constraint in Engineered Noncolinear Polyketide Assembly Lines . ChemBioChem . 10 . 7 . 1225–1232.