Genome-Based Discovery of Enantiomeric Pentacyclic Sesterterpenes Catalyzed by Fungal Bifunctional Terpene Synthases

Abstract

Genome-based discovery of two previously unreported fungal bifunctional terpene synthases (BFTSs) from phytopathogenic fungi are reported: FoFS catalyzing the formation of fusoxypenes A–C (1–3) and (−)-astellatene (4) and AtAS capable of synthesizing preaspterpenacid I (6). Interestingly, FoFS and AtAS catalyzed the formation of enantiomeric sesterterpenes with a 5–6–7–3–5 ring system. C22-oxidative modification of preaspterpenacid I by AtP450 was characterized as well. Plausible cyclization pathways of the fusoxypenes were illustrated by DFT calculations.

Mechanismus der bifunktionellen Multiprodukt‐Sesterterpensynthase AcAS aus Aspergillus calidoustus

“…In Klade I, die nur Sesterterpensynthasen enthält, reagiert das durch die Abspaltung von Pyrophosphat erzeugte Kation in einer 1,15‐14,18‐Cyclisierung unter Beteiligung der Olefinfunktionen der 4. und 5. Isoprenyleinheiten unter Bildung eines 5‐15‐bicyclischen Ringsystems, wie in der Biosynthese von Sesterfisherol durch NfSS, [1] Betaestacin I durch PbTS1, [3] Quiannulaten durch EvQS, [4] Sesterbrasiliatrien durch PbSS, [5] Fusoxypen A durch FoFS, [6] und Preaspterpensäure I durch AtAS [6] . In Klade II führen 1,11‐10,14‐Cyclisierungen durch Angriffe der 3. und 4.…”

Classifying Natural Products from Plants, Fungi or Bacteria using the COCONUT Database and Machine Learning

“…3). In details, the fungal epicospirocin 1 [33], penicimeroterpenoid A [34], beetleane A [35], funiculolide D [36], and fusoxypenes A [37], the bacterial vertirhodin A [38], bosamycin A [39], and dumulmycin [40], and the plant fortuneicyclidin A [41], meloyunnanine A [42], hyperfol B [43], pegaharmol A [44], hunzeylanine A [45], mucroniferal A [46], perovsfolin A [47], horienoid A [48], and erythrivarine J [49] were correctly classified. On the other hand, the fungal rhizolutin [50] and myxadazoles A [51] and the bacterial marinoterpin A [52] were misclassified.…”

Classifying Natural Products from Plants, Fungi or Bacteria using the COCONUT Database and Machine Learning

“…Among 20 recently reported NPs from plants, fungi, or bacteria, 17 were correctly assigned to their origin, while only two were misassigned (Table 3, Figure 3). In details, the fungal epicospirocin 1, [33] penicimeroterpenoid A, [34] beetleane A, [35] funiculolide D, [36] and fusoxypenes A, [37] the bacterial vertirhodin A, [38] bosamycin A, [39] and dumulmycin, [40] and the plant fortuneicyclidin A, [41] meloyunnanine A, [42] hyperfol B, [43] pegaharmol A, [44] hunzeylanine A, [45] mucroniferal…”