Macrotermycins A-D, Glycosylated Macrolactams from a Termite-Associated Amycolatopsis sp. M39

Abstract

Bioassay-guided metabolomic analyses led to the characterization of four new 20-membered glycosylated polyketide macrolactams, macrotermycins A-D, from a termite-associated actinomycete, Amycolatopsis sp. M39. M39's sequenced genome revealed the macrotermycin's putative biosynthetic gene cluster. Macrotermycins A and C had antibacterial activity against human-pathogenic Staphylococcus aureus and, of greater ecological relevance, they also had selective antifungal activity against a fungal parasite of the termite fungal garden.

Figure 1

A) Structures of macrotermycins A-D. B) Computational models of a macrotermycin B derivative, and C) of a macrotermycin D derivative calculated at the DFT B3LYP/6–31+G(d,p) level of theory without geometric constraints and supported by key NOE/ROE correlations (amino sugar moiety was replaced by a methoxy group to simplify calculations).

Figure 2

Organization of the putative macrotermycin biosynthetic gene cluster from Amycolatopsis sp. M39. A) Genetic map of the Mte gene cluster; each arrow represents the direction of transcription of open reading frame (ORF). B) Putative biosynthetic scheme of macrotermycin aglycone (5) formation.