Atrop-abyssomicin C

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Atrop-abyssomicin C
Names
IUPAC name
12,14a,3-(Epoxymethyno)-2H-1-benzoxacyclododecin-2,4,8(5H,10aH)-trione, 6,7,11,12,13,14-hexahydro-11-hydroxy-5,7,13-trimethyl-, (5R,7S,9E,10aR,11R,12R,13R,14aR)
Other names
Atrop-abyssomicin C
Identifiers
3D model (
JSmol
)
ChEMBL
ChemSpider
  • InChI=1S/C19H22O6/c1-8-6-9(2)14(21)13-17-19(25-18(13)23)7-10(3)16(24-17)15(22)11(19)4-5-12(8)20/h4-5,8-11,15-16,22H,6-7H2,1-3H3/b5-4+/t8-,9+,10+,11?,15+,16?,19+/m0/s1
    Key: FNEADFUPWHAVTA-WDQYZCCLSA-N
  • C[C@@H]1C[C@]23OC(=O)C4=C2OC1[C@H](O)C3\C=C\C(=O)[C@@H](C)C[C@@H](C)C4=O
Properties
C19H22O6
Molar mass 346.38 g/mol
Density 1.34±0.1 g/cm3 (Predicted)
Melting point 180 °C (decomp)
Boiling point 597.5±50.0 °C (Predicted)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Atrop-abyssomicin C is a polycyclic polyketide-type natural product that is the

Verrucosispora maris AB-18-032, a marine actinomycete found in sediment of the Japanese sea. They found that atrop-abyssomicin C was the major metabolite produced by this strain, while abyssomicin C was a minor product. The molecule displays antibacterial activity by inhibiting the enzyme PabB (4-amino-4-deoxychorismate synthase), thereby depleting the biosynthesis of p-aminobenzoate.[3][4]

Structure

Structure of Atrop-abyssomicin C and Abyssomicin C.

Atrop-abyssomicin C has a complex, yet intriguing structural topography. The compound contains an oxabicyclo[2.2.2]octane system fused to the tetronate moiety. The 11-membered macrocyclic ring carries an α,β-unsaturated ketone that was proposed to be the reactive center.[5] Despite being a strained macrocycle, there exist an atropisomer, abyssomicin C. The atropisomerism arise due to a structural deviation in the α,β-unsaturated ketone region of the molecule. The orientation of the carbonyl in atrop-abyssomicin C is cisoid, whereas the conformation in abyssomicin C is transoid.[6] The enone moiety of atrop-abyssomicin C has a higher degree of the conjugation, which makes it a more active Michael acceptor.[7]

Biosynthesis

The biosynthesis of atrop-abyssomicin C begins with the synthesis of a linear polyketide chain in a PKS I system that consist of one loading and six extension modules. The polyketide chain is made from five acetates, two propionates, and the glycolytic pathway metabolite. D-1,3-bisphosphoglycerate, the glycolytic metabolite, is transferred to AbyA3 (an acyl-carrier protein) by AbyA2 to generate the glyceryl-ACP. AbyA1 facilitates the attachment of the glyceryl-ACP to the polyketide chain and the detachment of the polyketide from the polyketide synthase to form intermediate 2.[7][8][9]

Biosynthesis of linear polyketide precursor. The AbyB1, AbyB2, and AbyB3 genes code for the seven-module polyketide synthase complex that assembled the polyketide backbone. Next, the linear polyketide precursor fused with glyceryl-ACP to form intermediate 2.

Based on the observation made for the biosynthesis of agglomerin, it has been proposed that AbyA4 acetylates intermediate 2 and AbyA5 catalyzes the elimination of acetic acid to form the exocyclic double bond in intermediate 4.[1] An intramolecular Diels-Alder was proposed to take place between the exocyclic olefin and the conjugated diene at the tail end of the polyketide to form the macrocyclic ring.[7] It has been reported that the previously unidentified Abycyc gene could code for an enzyme that carries out the Diels-Alder cycloaddition.[10] Following the Diels-Alder reaction, an epoxide ring is formed and then opened by the tetronate hydroxyl group to form atrop-abyssomicin C. It has been postulated that the AbyE monooxygenase catalyzes epoxide formation.[8]

Cycloaddition to form atrop-abyssomicin C. Intermediate 2 undergo an acetylation and elimination step to form the exocyclic olefin. An intramolecular Diels–Alder reaction is carried out to form the macrocyclic ring. Next, an oxygenation step follows by a ring opening reaction leads to atrop-abyssomicin C formation.

References

  1. ^
    PMID 23606658
    .
  2. PMID 16634106
    .
  3. PMID 17617698
    .
  4. PMID 17886307
    .
  5. PMID 20047014
    .
  6. PMID 17212423
    .
  7. ^
    doi:10.1016/B978-0-444-59603-1.00005-9
    .
  8. ^
    PMID 21656887
    .
  9. PMID 24965099
    .
  10. PMID 25551461
    .
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