Identification of a Key Prenyltransferase Involved in Biosynthesis of the Most Abundant Fungal Meroterpenoids Derived from 3,5‐Dimethylorsellinic Acid.

Abstract

Destroying aromaticity: A novel prenyltransferase (Trt2) involved in fungal meroterpenoid biosynthesis was shown to catalyze an unusual aromatic addition reaction onto a fully substituted aromatic ring. The prenylated product serves as a key intermediate in the biosynthesis of the most abundant series of meroterpenoids in fungi.

3,5‐Dimethylorsellinic Acid Derived Meroterpenoids from Eupenicillium sp. 6A‐9, a Fungus Isolated from the Marine Sponge Plakortis simplex

“…The biosynthesis of intriguing meroterpenoids metabolized by Aspergillus and Penicillium has been investigated for decades, and recently the molecular bases (biosynthetic genes/enzymes) for five 3,5-dimethylorsellinic acid (DMOA) and farnesyl pyrophosphate derived meroterpenoids, andrastin A, austinol, terretonin, anditomin, and berkeleydione, have been reported [20][21][22][23][24][25][26][27][28][29] and thoroughly reviewed. [30] Notably, the completely elucidated pathways for austinol [21,22,27] and berkeleydione, [29] for which the known compounds preaustinoid A1 (7) and preaustinoid A3 (10) acquired here are biosynthetic intermediates, enabled us to propose detailed mechanisms for the biosynthesis of the five related new meroterpenoids 1-5 (Scheme 1).…”

Meroterpenoids

“…13.3a ). The biosynthetic gene cluster for 17 , which consists of 13 genes (the trt cluster), was discovered in the genome database of A. terreus NIH 2624 [ 20 ]. The cluster was revised subsequently, because 4 of the 13 genes ( trt10 to trt13 ) are not actually involved in the biosynthesis of 17 and the requirement of one additional gene ( trt14 ) was found [ 21 ].…”

“…The gene, designated as ausA , encodes a type I PKS that synthesizes 14 from one molecule of acetyl-CoA and three molecules of malonyl-CoA, and is responsible for the production of 16 and dehydroaustinol ( 20 ). A subsequent gene disruption study was undertaken to identify the whole biosynthetic gene cluster for 16 and 20 (the aus cluster).…”

Genome Mining for Fungal Secondary Metabolic Gene Clusters

“…Genome sequences of several Aspergillus strains have recently enabled the discovery and heterologous reconstitution of a series of biosynthetic gene clusters involved in the biosynthesis of medicinally important meroterpenoids (e.g., pyripyropene [122], terretonin [123][124][125], fumagillin [126] (Fig. 4.1c), austinol, and dehydroaustinol [127]), which are polyketide-terpenoid hybrid compounds.…”