Uric Acid Is a Genuine Metabolite of Penicillium cyclopium and Stimulates the Expression of Alkaloid Biosynthesis in This Fungus

Abstract

On searching for endogenous, low-molecular-weight effectors of benzodiazepine alkaloid biosynthesis in Penicillium cyclopium uric acid was isolated from ethanolic or autoclaved mycelial extracts of this fungus. The isolation was based on a three-step high-pressure liquid chromatography procedure guided by a microplate bioassay, and uric acid was identified by mass spectrometry and the uricase reaction. Conidiospore suspensions that were treated with this compound during the early phase of outgrowth developed emerged cultures with an enhanced rate of alkaloid production. Uric acid treatment did not increase the in vitro measurable activity of the rate-limiting biosynthetic enzyme, cyclopeptine synthetase. However, these cultures displayed a reduced rate of uptake of the alkaloid precursor L-phenylalanine into the vacuoles of the hyphal cells as assayed in situ. It is suggested that the depressed capacity of vacuolar uptake caused by the contact of outgrowing spores with uric acid liberated from hyphal cells results in an enhanced availability of the precursor L-phenylalanine in the cytoplasm and thus accounts at least in part for the increase in alkaloid production.

HPLC-MS/MS Method for the Detection of Selected Toxic Metabolites Produced by Penicillium spp. in Nuts

“…Furthermore, CPN serves as a precursor for CPL, which explains the frequent co-occurrence of these extrolites in the matrices considered. CPN and CPL, as well as VIR, the latter detected in two samples out of 41 (almonds and walnuts), belong to the class of benzodiazepine alkaloids [55], and they have ecological significance due to their phytotoxic and antimicrobial properties [56,57]. Varga and colleagues [28] found VIR contamination in nut samples, with an incidence of 43% and a high contamination levels of MPA in hazelnuts and low contamination levels of CPA in almonds, recording an incidence of 47% and 13%, respectively.…”

Profiling microbial metabolomes: what do we stand to gain?

“…Most of the gene clusters for secondary metabolic biosynthesis appear to receive such signals at the respective pathway specific transcriptional activator genes via transcriptional activators (Horinouchi, 2002). Yet another metabolite, uric acid, has been shown to stimulate alkaloid biosynthesis in Penicillium cyclopium by indirect mechanisms (Helbig et al, 2002). Similarly, phosphate availability has been shown to regulate the biosynthesis of two antibiotics in Serratia (Slater et al, 2003).…”

The Effects of Bird Excrements on Copper and Bronze

“…Another study determined that uric acid can aid in the growth of penicillium cyclopium (Helbig, Steighardt, & Roos, 2002). Unfortunately, the only way to really distinguish fungal species is by sequencing.…”