Heterologe Produktion pilzlicher Maleidride enthüllt die kryptische Cyclisierung in ihrer Biosynthese

Williams, Katherine; Szwalbe, Agnieszka J.; Mulholland, Nicholas P.; Vincent, Jason L.; Bailey, Andy M.; Willis, Christine L.; Simpson, Thomas J.; Cox, Russell J.

doi:10.1002/ange.201511882

Cited by 11 publications

(11 citation statements)

References 29 publications

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“…In contrast, disruption of the PEBP gene (pvR1) to produce strains Agn∆pks-PV∆R1 led to a threefold reduction in titre of cornexistin 1 and the production of three previously reported 3,5 metabolites ( Figure 5D). Comparison of chromatographic and spectroscopic propertied confirmed that these were the monomer 5, its hydrolysis product 5' and 13 / 13' which arise by spontaneous decarboxylation of 5.…”

Section: Genementioning

confidence: 71%

“…This analysis showed that each of the key maleidride biosynthetic proteins encoded by the B. fulva cluster has a similar (> 38% identity) counterpart in the P. variotii cluster (see ESI). 5 Comparisons among all five clusters show that the hrPKS, hydrolase, CS, 2MCD, PEBP-like and KI-like genes occur in all clusters. The biosynthesis of 1, however, is expected to be more complex than that of 4, requiring removal of one maleic anhydride ring and several oxidative modifications.…”

mentioning

confidence: 97%

“…3 Related compounds include agnestadride A 2 (heptadride), 3 viburspiran 3 4 (octadride) and byssochlamic acid 4 (nonadride). 3,5 Maleic anhydrides have been associated with a wide range of useful biological properties. 6 We recently elucidated the complete biosynthetic pathway of byssochlamic acid 4.…”

mentioning

confidence: 99%

“…6 We recently elucidated the complete biosynthetic pathway of byssochlamic acid 4. 5 The first step of the pathway is catalysed by a fungal highly reducing polyketide synthase (hrPKS), 7 and subsequent steps involve a citrate synthase (CS) homologue and a 2methyl citrate dehydratase (2MCD) to create the key intermediate 5. Oikawa also reported a similar early pathway towards the phomoidrides 8 and Tang and coworkers have shown that the biosynthesis of rubratoxins follows the same pathway.…”

mentioning

confidence: 99%

“…Predicted coding sequences were annotated using BLAST and InterPro (Table 1). The putative cornexistin 1 BGC 11 was compared to the previously identified byssochlamic acid BGC, 5 as well as to two putative maleidride BGCs from Talaromyces stipitatus and one identified from several Cochliobolus species, using Artemis (see ESI).…”

mentioning

confidence: 99%

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Genetic and chemical characterisation of the cornexistin pathway provides further insight into maleidride biosynthesis

et al. 2017

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The biosynthesis of the herbicide cornexistin in the fungus Paecilomyces variotii was investigated by full sequencing of its genome, knockout of key genes within its biosynthetic gene cluster and isolation and identification of intermediate compounds. The general biosynthetic pathway resembles that of byssochlamic acid and other nonadrides in the early stages, but differs in requiring fewer enzymes in the key nonadride dimerisation step, and in the removal of one maleic anhydride moiety.

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Section: Genementioning

confidence: 71%

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confidence: 97%

mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Genetic and chemical characterisation of the cornexistin pathway provides further insight into maleidride biosynthesis

et al. 2017

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A Cascade of Redox Reactions Generates Complexity in the Biosynthesis of the Protein Phosphatase‐2 Inhibitor Rubratoxin A

et al. 2017

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Redox modifications are key complexity‐generating steps in the biosynthesis of natural products. The unique structure of rubratoxin A (1), many of which arise through redox modifications, make it a nanomolar inhibitor of protein phosphatase 2A (PP2A). We identified the biosynthetic pathway of 1 and completely mapped the enzymatic sequence of redox reactions starting from the nonadride 5. Six redox enzymes are involved, including four α‐ketoglutarate‐ and iron(II)‐dependent dioxygenases that hydroxylate four sp3 carbons; one flavin‐dependent dehydrogenase that is involved in formation of the unsaturated lactone; and the ferric‐reductase‐like enzyme RbtH, which regioselectively reduces one of the maleic anhydride moieties in rubratoxin B to the γ‐hydroxybutenolide that is critical for PP2A inhibition. RbtH is proposed to perform sequential single‐electron reductions of the maleic anhydride using electrons derived from NADH and transferred through a ferredoxin and ferredoxin reductase pair.

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Total Synthesis of (+)‐Cornexistin

et al. 2020

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Herein, we describe the first total synthesis of (+)‐cornexistin as well as its 8‐epi‐isomer starting from malic acid. The robust and scalable route features a Nozaki–Hiyama–Kishi reaction, an auxiliary‐controlled syn‐Evans‐aldol reaction, and a highly efficient intramolecular alkylation to form the nine‐membered carbocycle. The delicate maleic anhydride moiety of the nonadride skeleton was constructed from a β‐keto nitrile. The developed route enabled the synthesis of 165 mg (+)‐cornexistin.

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Heterologe Produktion pilzlicher Maleidride enthüllt die kryptische Cyclisierung in ihrer Biosynthese

Cited by 11 publications

References 29 publications

Genetic and chemical characterisation of the cornexistin pathway provides further insight into maleidride biosynthesis

Genetic and chemical characterisation of the cornexistin pathway provides further insight into maleidride biosynthesis

A Cascade of Redox Reactions Generates Complexity in the Biosynthesis of the Protein Phosphatase‐2 Inhibitor Rubratoxin A

Total Synthesis of (+)‐Cornexistin

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