Aureothin

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| ImageFile = Aureothin.png

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| IUPACName = 2-methoxy-3,5-dimethyl-6-[(2R,4Z)-4-[(E)-2-methyl-3-(4-nitrophenyl)prop-2-enylidene]oxolan-2-yl]pyran-4-one{{cite web |title=Aureothin |website= Pubchem |url=https://pubchem.ncbi.nlm.nih.gov/compound/Aureothin#section=Canonical-SMILES |language=en}}

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| CASNo = 2825-00-5

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| ChEBI = 80024

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| ChemSpiderID = 5029106

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| KEGG = C15689

| PubChem = 6569946

| UNII = G359FGQ2RB

| StdInChI=1S/C22H23NO6/c1-13(9-16-5-7-18(8-6-16)23(25)26)10-17-11-19(28-12-17)21-14(2)20(24)15(3)22(27-4)29-21/h5-10,19H,11-12H2,1-4H3/b13-9+,17-10-/t19-/m1/s1

| StdInChIKey = GQKXCBCSVYJUMI-WACKOAQBSA-N

| SMILES = CC1=C(OC(=C(C1=O)C)OC)[C@H]2C/C(=C/C(=C/C3=CC=C(C=C3)[N+](=O)[O-])/C)/CO2

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| Section2 = {{Chembox Properties

| C=22 | H=23 | N= 1 | O=6

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| Section3 = {{Chembox Hazards

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| synonyms = (+)-aureothin

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Aureothin is a natural product of a cytotoxic shikimate-polyketide antibiotic with the molecular formula C₂₂H₂₃NO₆.{{cite book |title=Issues in Chemistry and General Chemical Research |edition=2011 |date=9 January 2012 |publisher=ScholarlyEditions |isbn=978-1-4649-6334-6 |pages=442}}{{cite journal |last1=He |first1=Jing |last2=Hertweck |first2=Christian |title=Biosynthetic Origin of the Rare Nitroaryl Moiety of the Polyketide Antibiotic Aureothin: Involvement of an Unprecedented N-Oxygenase |journal=Journal of the American Chemical Society |date=1 March 2004 |volume=126 |issue=12 |pages=3694–3695 |doi=10.1021/ja039328t|pmid=15038705 }} Aureothin is produced by the bacterium Streptomyces thioluteus{{cite journal |last1=Hirata |first1=Yoshimasa |last2=Nakata |first2=Hisao |last3=Yamada |first3=Kiyoyuki |last4=Okuhara |first4=Kunio |last5=Naito |first5=Takayuki |title=The structure of aureothin, a nitro compound obtained from Streptomyces thioluteus |journal=Tetrahedron |date=January 1961 |volume=14 |issue=3–4 |pages=252–274 |doi=10.1016/S0040-4020(01)92175-1}} that illustrates antitumor, antifungal, and insecticidal activities and the new aureothin derivatives can be antifungal and antiproliferative. In addition, aureothin, a nitro compound from Streptomyces thioluteus, was indicated to have pesticidal activity against the bean weevil{{Cite journal |last1=Oishi |first1=H. |last2=Hosokawa |first2=T. |last3=Okutomi |first3=T. |last4=Suzuki |first4=K. |title=Pesticidal Activity of Aureothin |url=https://doi.org/10.1080/00021369.1969.10859541 |journal=Agricultural and Biological Chemistry |year=1969 |volume=33 |issue=12 |pages=1790–1791|doi=10.1080/00021369.1969.10859541 |url-access=subscription }} by interfering with mitochondrial respiratory complex II.{{Cite journal |last1=Friedrich |first1=T |last2=Van Heek |first2=P |last3=Leif |first3=H |last4=Ohnishi |first4=T |last5=Forche |first5=E |last6=Kunze |first6=B |last7=Jansen |first7=R |last8=Trowitzsch-Kienast |first8=W |last9=Hofle |first9=G |last10=Reichenhach |first10=H |title=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 |journal=Eur. J. Biochem. |year=1994 |volume=219 |issue=1 |pages=691–698|doi=10.1111/j.1432-1033.1994.tb19985.x |pmid=8307034 |doi-access=free }}

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.{{Cite journal |last1=He |first1=Jing |last2=Hertweck |first2=Christian |title=Biosynthetic Origin of the Rare Nitroaryl Moiety of the Polyketide Antibiotic Aureothin: Involvement of an Unprecedented N-Oxygenase |url=https://pubs.acs.org/doi/pdf/10.1021/ja039328t |journal=J. Am. Chem. Soc. |year=2004 |volume=126 |issue=12 |pages=3694–3695|doi=10.1021/ja039328t |pmid=15038705 |url-access=subscription }} 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.{{Cite journal |last1=Tsunematsu |first1=Yuta |last2=Hirayama |first2=Yuichiro |last3=Masuya |first3=Takahiro |last4=Watanabe |first4=Kenji |title=Oxidative Modification Enzymes in Polyketide Biosynthetic Pathways |url=https://www.sciencedirect.com/science/article/pii/B9780124095472146372 |journal=Comprehensive Natural Products III (Third Edition) |year=2020 |volume=1 |pages=479–505|doi=10.1016/B978-0-12-409547-2.14637-2 |isbn=9780081026915 |s2cid=201202729 |url-access=subscription }} 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{{Cite journal |last1=He |first1=Jing |last2=Hertweck |first2=Christian |title=Functional Analysis of the Aureothin Iterative Type I Polyketide Synthase |url=https://doi.org/10.1002/cbic.200400333 |journal=ChemBioChem |year=2005 |volume=6 |issue=5 |pages=908–912|doi=10.1002/cbic.200400333 |pmid=15812854 |s2cid=27585538 |url-access=subscription }} 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).{{Cite journal |last1=He |first1=Jing |last2=Hertweck |first2=Christian |title=Biosynthetic Origin of the Rare Nitroaryl Moiety of the Polyketide Antibiotic Aureothin: Involvement of an Unprecedented N-Oxygenase |url=https://pubs.acs.org/doi/10.1021/ja039328t |journal=J. Am. Chem. Soc. |year=2004 |volume=126 |issue=12 |pages=3694–3695|doi=10.1021/ja039328t |pmid=15038705 |url-access=subscription }} 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.{{Cite journal |last1=Sugimoto |first1=Yuki |last2=Ishida |first2=Keishi |last3=Traitcheva |first3=Nelly |last4=Busch |first4=Benjamin |last5=Dahse |first5=Hans-Martin |last6=Hertweck |first6=Christian |title=Freedom and Constraint in Engineered Noncolinear Polyketide Assembly Lines |url=https://www.cell.com/ccbio/pdfExtended/S1074-5521(15)00004-6 |journal=ChemBioChem |volume=10 |issue=7 |pages=1225–1232}}

File:Biosynthesis of Aureothin.png

Aureothin

Biosynthesis

References

Further reading