Fungal cyclooligomerdepsipeptides: From classical biochemistry to combinatorial biosynthesis

Abstract

This review surveys the biological activities and the iterative and recursive biosynthetic mechanisms of fungal cyclooligomer depsipeptides, and their structural diversification by various combinatorial biosynthetic methods.

Beauvericin production by the Lepidoptera pathogenic fungus Isaria tenuipes: Analysis of natural specimens, synnemata from cultivation, and mycelia from liquid-media fermentation

“…1 Beauvericin and related fungal cyclooligomer depsipeptides, enniatins, were also reported as inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT) 2 and the human immunodeficiency virus type-1 integrase. 3 Beauvericin was first described from an entomopathogenic fungus Beauveria bassiana on the basis of its toxicity to brine shrimp.…”

“…Indeed, beauvericin is known to be cytotoxic to human cells, and it has been considered as one of the problem toxins produced by Fusarium species in crops. 1,22 In addition, we were also interested in whether or not beauvericin is present in natural specimens of Isaria tenuipes. We therefore undertook quantitative analysis of beauvericin in three different forms of Isaria tenuipes from the same natural source: (a) natural specimen (synnemata and insect cadaver), (b) synnemata cultivated on rice, and (c) mycelia of liquid-media fermentation broth.…”

In vitro chemoenzymatic and in vivo biocatalytic syntheses of new beauvericin analogues

“…CODs are produced by nonribosomal peptide synthetase (NRPS) enzymes in an iterative and recursive process. 4,8 Beauvericin synthetase (BbBEAS) contains two NRPS modules harbouring domains that catalyze adenylation (A), thiolation (T), methylation (M) and condensation (C) reactions. The A domains activate their dedicated substrates (A 1 : D-2-hydroxyisovalerate [D-Hiv]; A 2 : L-phenylalanine [L-Phe]) by aminoadenylation, followed by covalent loading of these substrates onto BbBEAS for subsequent assembly of beauvericin.…”

“…The A domains activate their dedicated substrates (A 1 : D-2-hydroxyisovalerate [D-Hiv]; A 2 : L-phenylalanine [L-Phe]) by aminoadenylation, followed by covalent loading of these substrates onto BbBEAS for subsequent assembly of beauvericin. 4,[9][10][11] The beauvericin precursor D-Hiv is synthesized by ketoisovalerate reductase (KIVR) from 2-ketoisovalerate from primary metabolism. 4,12,13 In this contribution we demonstrate, for the first time, the isolation of recombinant beauvericin synthetase BbBEAS (351 kDa, B0.4 mg mL…”

Diversity and Ecological Significance of Fungal Endophyte Natural Products

“…There is a tremendous structural variety of non-ribosomal peptides biosynthesized by fungi, mainly based on the flexibility of the biosynthetic programming of NRPSs, with adenylation domains responsible for activating a wide variety of nonproteinogenic amino acids, and the formation of main chain heterocycles and linear, macrocyclic, or branched macrocyclic structures with amide, ester, or thioester closure [68]. However, despite their production by many filamentous fungi, few have been described in endophytic fungi and their biological activities are still underexplored.…”