Biosynthesis of Territrems by Aspergillus terreus

Abstract

Different radioactive precursors were added to 8-day potato-dextrose liquid cultures of Aspergillus terreus 23-1. Territrems were isolated from chloroform extracts of the cultures at day 14 and purified by thin-layer chromatography and high-pressure liquid chromatography. The territrem B obtained was treated with alkaline hydrogen peroxide, and 3, 4, 5-trimethoxy benzoic acid was isolated from an ethyl acetate extract of the reaction mixture and purified by thin-layer chromatography and high-pressure liquid chromatography. By comparison of the specific radioactivities of territrem B and its cleaved aromatic product (disintegrations per minute per micromole of compound), it was demonstrated that the radioactivity of territrem B was located mainly on its aromatic moiety when [U- 14 C]shikimate, l -[ methyl - 14 C]methionine, and l -[ methyl - 3 H]methionine were precursors; however, the radioactivity of territrem B was located mainly on its nonaromatic moiety when [2- 14 C]mevalonate was the precursor. Mevinolin, a specific inhibitor of β-hydroxyl β-methyl glutaryl coenzyme A reductase, was shown to inhibit production of territrems by A. terreus 23-1. When [U- 14 C]acetate was used as a precursor, mevinolin inhibited the incorporation of radioactive carbon into territrem but mevinolin did not inhibit incorporation of radioactive carbon from [2- 14 C]mevalonate into territrem.