Biosynthesis of the Unusual Epoxy Isonitrile-Containing Antibiotics Aerocyanidin and Amycomicin.

Aerocyanidin and amycomicin are two antibiotics derived from long-chain acids with a rare epoxy isonitrile moiety, the complexity of which renders the total synthesis of these two natural products rather challenging. How this functionality is biosynthesized has also remained obscure. While the biosynthetic gene clusters for these compounds have been identified, both appear to be deficient in genes encoding enzymes seemingly necessary for the oxidative modifications observed in these antibiotics. Herein, the biosynthetic pathways of aerocyanidin and amycomicin are fully elucidated. They share a conserved pathway to isonitrile intermediates that involves a bifunctional thioesterase and a nonheme iron α-ketoglutarate-dependent enzyme. In both cases, the isonitrile intermediates are then loaded onto an acyl carrier protein (ACP) catalyzed by a ligase. The isonitrile-tethered ACP is subsequently processed by polyketide synthase(s) to undergo chain extension, thereby assembling a long-chain γ-hydroxy isonitrile acid skeleton. The epoxide is installed by the cupin domain-containing protein AecF to conclude the biosynthesis of aerocyanidin. In contrast, three P450 enzymes AmcB, AmcC, and AmcQ are involved in epoxidation and keto formation to finalize the biosynthesis of amycomicin. These results thus explain the sequence of oxidation events that result in the final structures of aerocyanidin and amycomicin as well as the biosynthesis of the key γ-hydroxy epoxy isonitrile functional group.

Iridoid and phenylethanoid glycosides from the aerial part of Barleria lupulina

Abstract A new iridoid glycoside, barlupulin C methyl ester (1), together with two known phenylethanoid glycosides (2 and 3) and three known simple phenolic glycosides (4-6) were isolated from the aerial parts of Barleria lupulina Lindl., Acanthaceae. The structure of the new compound (1) was elucidated through 1D and 2D NMR spectroscopic data, and HR-ESIMS. Interestingly, compound (1) has a formate group attached to the C-6 hydroxy group of the glucose unit. Compounds 2-6 were identified as poliumoside (2), decaffeoylacteoside (3), protocatechuic acid 4-O-β-glucoside (4), vanillic acid 4-O-β-glucoside (5), and leonuriside A (6) on the basis of NMR spectroscopic data analyses and comparison with those reported in the literature. Compounds 3-6 were isolated from B. lupulina for the first time.