Abyssomicin Biosynthesis: Formation of an Unusual Polyketide, Antibiotic‐Feeding Studies and Genetic Analysis

Abstract

Small wonder: Atrop‐abyssomicin C is a small, yet complex spirotetronate (see scheme) that is active against Gram‐positive bacteria, such as MRSA. Feeding studies and genetic manipulation of its producer, Verrucosispora maris AB‐18‐032, for the first time give insight into its biosynthesis and demonstrate how closely related the members of this important class of molecules are.

A twist of nature – the significance of atropisomers in biological systems

“…Comparison with other biosynthetic studies of tetronate antibiotics aided in the identification of genes responsible for abyssomicin C biosynthesis; three genes encoding for proteins for the generation of the polyketide backbone (which effectively forms the macrocycle in abyssomicin C); five genes encoding for proteins involved in the generation of the tetronate moiety; three genes for further oxidative enzymes; and a variety of other genes related to import, export and packaging of the molecule. 57 It was noted that the structure of 23 and 24 were similar to that of chorismate, a precursor to PABA, 58 and studies revealed that atrop-abyssomicin irreversibly binds the Cys263 of E. coli 4-amino-4-deoxychorismate in a Michael addition, forming a sulphur-bound abyssomicin D in the process. 47 This mechanism is attributed to the α,β-unsaturated ketone, which is not present in other detected abyssomicins.…”

Tetrodecamycin: An unusual and interesting tetronate antibiotic

“…Based on a similar reaction which has been suggested for abyssomicin (Fig. 1B), 71 we propose that the cyclization resulting in this heterocyclic ring would proceed through two steps. First, the alkene present at C-14/C-15 in intermediate 12 would undergo an epoxidation giving intermediate 13.…”

Marine Microbial Secondary Metabolites

“…PKS domains are shown as circles. Adapted from Gottardi et al (2011). which follow have the same basic set, each extended by DH and KR domains arranged in the biosynthetic assembly line. Module 5 of abyB2 has the same arrangement of module 4, but the DH and KR domains are likely to be inactive.…”

“…There are also genes encoding oxygenases, as well as genes with putative regulatory and export functions involved in the abyssomicin biosynthesis. Formation of abyssomicin C requires two propionates, five acetates and one glucose-derived metabolite (Gottardi et al, 2011).…”

“…Module 5 of abyB2 has the same arrangement of module 4, but the DH and KR domains are likely to be inactive. Module 6 contains an additional ER domain, and module 7 of protein AbyB3 has an additional acetate unit (Gottardi et al, 2011).…”