Atrop-abyssomicin C

Atrop-abyssomicin C is a polycyclic polyketide-type natural product that is the atropisomer of abyssomicin C. It is a spirotetronate that belongs to the class of tetronate antibiotics, which includes compounds such as tetronomycin, agglomerin, and chlorothricin.

The molecule displays antibacterial activity by inhibiting the enzyme PabB (4-amino-4-deoxychorismate synthase), thereby depleting the biosynthesis of p-aminobenzoate.

[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.

[7] 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.

[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.

Structure of Atrop-abyssomicin C and Abyssomicin C.
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 .
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.