The biosynthesis of pramanicin in Stagonospora sp. ATCC 74235: a modified acyltetramic acid†

Abstract

Biosynthetic incorporations of acetate, malonate and serine precursors which had been isotopically labelled with 2H, 13C, 15N and 18O into pramanicin 1 in Stagonospora sp. ATCC 74235 were demonstrated. Intact incorporation of a starter acetate and six extender malonates generates the acyclic, hydrophobic tail. A further intact acetate, in preference to malonate, and a serine entity which is incorporated only as the L-enantiomer and with the OC–CH(N)–CH2 entity intact, provide the pyrrolidone ring and hydroxymethyl group of 1. The results are fully consistent with a biosynthetic pathway involving an acyltetramic acid (2). The olefinic precursor 3 of the epoxide in 1 is described, and is also shown to co-occur in the cultures. The ratio of 1∶3 can be controlled by addition of precursors.