The sporothriolides. A new biosynthetic family of fungal secondary metabolites

Tian, Dong-Song; Kuhnert, Eric; Ouazzani, Jamal; Wibberg, Daniel; Kalinowski, Jörn; Cox, Russell J.

doi:10.1039/d0sc04886k

Cited by 18 publications

(39 citation statements)

References 33 publications

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“…We, [20,21] and others, [22] have shown that reconstruction of cryptic fungal biosynthetic pathways in the host organism Aspergillus oryzae NSAR1 is an effective way to understand complex transformations. Here, we deploy those methods and in vitro studies of isolated enzymes aiming to overcome the hurdles that have previously hampered characterization of pathway intermediates during the biosynthesis of these intriguing metabolites [3] …”

Section: Introductionmentioning

confidence: 99%

Early Oxidative Transformations During the Biosynthesis of Terrein and Related Natural Products

Kahlert

Bernardi

Hauser

et al. 2021

Chemistry A European J

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The mycotoxin terrein is derived from the C10‐precursor 6‐hydroxymellein (6‐HM) via an oxidative ring contraction. Although the corresponding biosynthetic gene cluster (BGC) has been identified, details of the enzymatic oxidative transformations are lacking. Combining heterologous expression and in vitro studies we show that the flavin‐dependent monooxygenase (FMO) TerC catalyzes the initial oxidative decarboxylation of 6‐HM. The reactive intermediate is further hydroxylated by the second FMO TerD to yield a highly oxygenated aromatic species, but further reconstitution of the pathway was hampered. A related BGC was identified in the marine‐derived Roussoella sp. DLM33 and confirmed by heterologous expression. These studies demonstrate that the biosynthetic pathways of terrein and related (polychlorinated) congeners diverge after oxidative decarboxylation of the lactone precursor that is catalyzed by a conserved FMO and further indicate that early dehydration of the side chain is an essential step.

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Section: Introductionmentioning

confidence: 99%

Early Oxidative Transformations During the Biosynthesis of Terrein and Related Natural Products

Kahlert

Bernardi

Hauser

et al. 2021

Chemistry A European J

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“…A separation by Supercritical Fluid Chromatography on chiral stationary phase allowed us the obtaining and characterization of the enantiomerically natural pure (+)-antipode. While we recently contributed to the elucidation of the biosynthesis pathway of the sporothriolide 1, [35] the biosynthesis of the trienylfuranol A 2 and sporochartines 3 remains to be elucidated, in particular the involvement of a Diels-Alder type reaction. We will benefit from the…”

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confidence: 99%

Total Synthesis of the Fungal Metabolite Trienylfuranol A through Nucleophilic Diastereodivergent Additions to Oxocarbenium Ions

et al. 2021

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Herein, we describe the first total synthesis of trienylfuranol A, a fungal triene-substituted tetrahydrofuran metabolite. The stereoselectivity of the chiral center bearing the trienyl side chain was diastereodivergently controlled by the addition of nucleophilic species on substituted γ-butyrolactone. Remarkably, the C-nucleophilic species or hydride addition onto oxocarbenium intermediate leads to the opposite diastereoselectivity reported for Kishi or Woerpel models. The use of Hantzsch ester (HEH) as organic hydride donor has enabled us to obtain the desired stereochemistry. The total synthesis of trienylfuranol A was achieved in 8 steps from acetaldehyde and pyruvic acid.

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“…This release mechanism differs from that used by fungal FAS (e.g. SpoFas) 3 where the malonyl-palmitoyl transferase (MPT) domain is known to both load malonyl CoA extenders, and release products directly as CoA thiolesters. 38 The next step of the pathway is also closely related to primary metabolism.…”

Section: Discussionmentioning

confidence: 89%

In vitro studies of maleidride-forming enzymes

et al. 2021

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The sporothriolides. A new biosynthetic family of fungal secondary metabolites

Abstract: The biosynthetic gene cluster of the antifungal metabolite sporothriolide 1 was identified from three producing ascomycetes: Hypomontagnella monticulosa MUCL 54604, H. spongiphila CLL 205 and H. submonticulosa DAOMC 242471. A...

Cited by 18 publications

References 33 publications

Early Oxidative Transformations During the Biosynthesis of Terrein and Related Natural Products

Early Oxidative Transformations During the Biosynthesis of Terrein and Related Natural Products

Total Synthesis of the Fungal Metabolite Trienylfuranol A through Nucleophilic Diastereodivergent Additions to Oxocarbenium Ions

In vitro studies of maleidride-forming enzymes

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