Reconstituted biosynthesis of fungal meroterpenoid andrastin A

Rapid Reconstitution of Biosynthetic Machinery for Fungal Metabolites in Aspergillus oryzae: Total Biosynthesis of Aflatrem

“…Recently, the use of the A. oryzae expression system was further extended to reconstitute the biosynthetic machinery for fungal secondary metabolites. To date, de novo syntheses of tenellin (four genes),12 aphidicolin (four genes),13 paxilline (six genes),14 and aspyridone (three genes)15 in A. oryzae have been reported, as well as the syntheses of the pyripyropene core structure (2+3 genes)16 and andrastin (5+4 genes) 17. The successful demonstration of the total biosynthesis of various types of natural products and stepwise determination of biosynthetic intermediates show the feasibility of using the A. oryzae reconstitution system for the biosynthetic study of fungal metabolites.…”

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).…”

Terpenoid Biosynthesis Off the Beaten Track: Unconventional Cyclases and Their Impact on Biomimetic Synthesis

“…Proposed mechanisms for the cyclization of epoxyfarnesyl-DMOA methyl ester (30) to protoaustinoid A (31), preterretonin A (32), [36] and andrastin E (33), [37] catalyzed by AusL, Trt1, and AdrI, respectively, depending on the position of proton abstraction from the shared tetracyclic carbocationic intermediate. Proposed mechanisms for the cyclization of epoxyfarnesyl-DMOA methyl ester (30) to protoaustinoid A (31), preterretonin A (32), [36] and andrastin E (33), [37] catalyzed by AusL, Trt1, and AdrI, respectively, depending on the position of proton abstraction from the shared tetracyclic carbocationic intermediate.…”

“…[36] In a very similar approach, AdrI was also shown to be involved as a MTC in the biosynthesis of andrastin A. [37] These compounds are derived from 3,5dimethylorsellinic acid (DMOA) and FPP, and their biosyntheses share epoxyfarnesyl-DMOA methyl ester (30) as a common intermediate (Scheme 9). The different outcomes of the AusL, Trt1, and AdrI reactions, which yield protoaustinoid A (31), preterretonin A (32), and andrastin E (33), respectively, depends on the preference of the respective MTC for the position of proton abstraction from the shared tetracyclic carbocationic intermediate.…”