Identification of Intermediates in the Biosynthesis of PR Toxin by Penicillium roqueforti

Abstract

The sesquiterpenoid 7-epi-neopetasone was synthesized via the Wieland-Miescher ketone. The compound was identical to a previously tentatively identified headspace constituent of Penicillium roqueforti. Feeding experiments with (13) C-labeled mevalonolactone isotopomers demonstrated that oxidation at C12 and an isomerization of the C11C12 to a C7C11 double bond must occur independently and not via a C7-C11-C12 allyl radical in one step. Feeding with (11,12,13-(13) C3 )-7-epi-neopetasone resulted in labelling of the PR toxin, thus establishing this compound as a newly identified pathway intermediate.

Two separate key enzymes and two pathway‐specific transcription factors are involved in fusaric acid biosynthesis in Fusarium fujikuroi

“…However, GC‐MS analysis of ethyl acetate extracts showed no incorporation of labelling into FSA. Investigation of the crude extract by 13 C‐nuclear magnetic resonance (NMR) spectroscopy, a technique that allows for a very sensitive detection of the incorporation of 13 C‐labellings in case of low incorporation rates (Riclea and Dickschat, ), revealed incorporation of 13 C‐labelling with very low rates ( c . 1%) by the occurrence of small satellite signals due to 13 C, 13 C‐couplings (http://onlinelibrary.wiley.com/doi/10.1111/1462-2920.13150/suppinfo).…”

Total Synthesis of the Polyoxygenated Sesquiterpenes Guignarderemophilanes C and D

“…Upon elimination of water, we now had octalone 32 in hand and addressed the installation of the isopropenyl group for targeting the sesquiterpene skeleton. Similar procedures on octalones using a two‐step procedure have already been described in literature: first, aldol addition to acetone gives the tertiary alcohol, which is then dehydrated regioselectively using Burgess reagent . For the aldol step, we had to slightly modify the literature procedure and add the acetone to the enolate at −40 °C, as previous experiments had shown no conversion and full recovery of starting material when the electrophile was added at −78 °C.…”

PR Toxin – Biosynthesis, Genetic Regulation, Toxicological Potential, Prevention and Control Measures: Overview and Challenges

“…The biosynthesis of PR toxin leads into formation of several other related and intermediate compounds such as eremophortins A, B, C, and D as revealed by the recent evidences on enzymes encoded by PR toxin gene clusters related to PR toxin named eremofortin A (EreA), eremofortin B (EreB), eremofortin C (EreC) and a tricyclic by product eremofortin D (EreD) an intermediate compound, formed in the biosynthetic route targeting for production of PR toxin ( Moreau et al, 1980 ), and was also revealed from the enzymatic studies done on PR gene clusters ( Figure 2 ; Hidalgo et al, 2014 ). In fact, new intermediates have been found and reported in the biosynthetic route available for PR toxin in P. roqueforti ( Riclea and Dickschat, 2015 ). However, the biochemical conversion of eremophortin C to PR toxin could also be achieved through the activity of eremophortin C specific oxidases (EC).…”

“…Among these, only PR toxin is lethal and can cause a wide range of short-term as well as long-term ill-effects in organisms, ranging from immediate or delayed toxic response to potentially adverse long-term carcinogenic effects in animals such as rats, mice, and cats ( Wei et al, 1975 , 1976 ; Chen et al, 1982 ). It is worth mentioning that in spite of being well known for its acute toxicity, only a few toxicity data and its implicated mechanism are available in the literature ( Hidalgo et al, 2014 , 2017 ; Riclea and Dickschat, 2015 ; García-Estrada and Martín, 2016 ). Previous studies reveal that PR toxin is lethal to rodents after administered orally (p.o.…”

“…The commercially exploited strains of P. roqueforti used as starter cultures and other those recovered from blue cheeses have the ability to produce PR toxin ( Orth, 1976 ; Wei and Liu, 1978 ; Engel and Prokopek, 1979 ; Medina et al, 1984 ; Chang et al, 1991 ; Boysen et al, 1996 ; Geisen et al, 2001 ). Noteworthy, the microaerophilic conditions and presence of nitrogen compounds such as amino acids, casein, amines and ammonium salts provides the unstable condition for the production of PR toxin in blue cheeses, which presumably degraded to various derivatives, namely PR acid, PR imine and PR amide, that are considered as less toxic molecules ( Vallone et al, 2014 ; Hidalgo et al, 2014 ; Riclea and Dickschat, 2015 ). These compounds, unlike the PR toxin and its Ere derivatives, can be found in blue cheeses ( Moreau et al, 1980 ; Chang et al, 1993 ).…”