Abyssomicins-A 20-Year Retrospective View

Abstract

Abyssomicins represent a new family of polycyclic macrolactones. The first described compounds of the abyssomicin family were abyssomicin B, C, atrop-C, and D, produced by the marine actinomycete strain Verrucosispora maris AB-18-032, which was isolated from a sediment collected in the Sea of Japan. Among the described abyssomicins, only abyssomicin C and atrop-abyssomicin C show a high antibiotic activity against Gram-positive bacteria, including multi-resistant and vancomycin-resistant strains. The inhibitory activity is caused by a selective inhibition of the enzyme 4-amino-4-deoxychorismate synthase, which catalyzes the transformation of chorismate to para-aminobenzoic acid, an intermediate in the folic acid pathway.

Keywords: 4-amino-4-deoxychorismate synthase inhibitor; abyssomicins; chorismate pathway.

Figure 1

The bacterial chorismate biosynthetic pathway.

Figure 2

Structures of abyssomicin C and atrop-abyssomicin C produced by Verrucosispora maris AB-18-032.

Figure 3

HPLC analysis of a culture filtrate extract from strain AB-18-032 at a fermentation time of 96 h, monitored at 260 nm. Inserts: UV-visible spectra of abyssomicin B, co-eluted C and atrop-C, and D. Reused with permission from [2], copyright owned by Japan Antibiotics Research Association.

Figure 4

Structures of abyssomicins produced by Verrucosispora maris AB-18-032.

Figure 5

Similarity of the diaxial conformation of chorismate with the abyssomicin C core.

Figure 6

Scanning electron micrograph of Verrucosispora sp. AB-18-032. Bar: 1 µm. Reused with permission from [2], copyright owned by Japan Antibiotics Research Association.

Figure 7

Neighbor-joining phylogenetic tree based on nearly complete 16S rDNA sequences of members of the suborder Micromonosporineae. Reused with permission from [2], copyright owned by Japan Antibiotics Research Association.