Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

Abstract

A pair of geometrically isomeric unsaturated keto fatty acids, (6E,8Z)- and (6E,8E)-5-oxo-6,8-tetradecadienoic acids (1 and 2), were isolated from the culture broth of an actinomycete of the genus Micrococcus, which was associated with a stony coral, Catalaphyllia sp. Their chemical structures were elucidated by spectroscopic analysis including NMR and MS, with special assistance of spin system simulation studies for the assignment of an E geometry at C8 in 2. As metabolites of microbes, compounds 1 and 2 are unprecedented in terms of bearing a 2,4-dienone system. Both 1 and 2 showed antibacterial activity against the plant pathogen Rhizobium radiobacter and the fish pathogen Tenacibaculum maritimum, with a contrasting preference that 1 is more effective to the former strain while 2 is so to the latter. In addition, compounds 1 and 2 displayed agonistic activity against peroxisome proliferator-activated receptors (PPARs) with an isoform specificity towards PPARα and PPARγ.

Keywords: Micrococcus; PPAR; antibacterial; coral; keto fatty acid.

Figure 1

Structures of (6E,8Z)- and (6E,8E)-5-oxo-6,8-tetradecadienoic acids (1 and 2).

Figure 2

COSY and key HMBC correlations for 1 and 2.

Figure 3

Spin system simulation for the C8–C9 double bond of 2.

Figure 4

Natural keto fatty acids of various origins.

Figure 5

PPAR activation by 1 and 2.