Developed network between taxoid and phenylpropanoid pathways in Cryptosporiopsis tarraconensis, taxan-producing endophytic fungus by Debiased Sparse Partial Correlation (DSPC) algorithm

Abstract

Although bioproduction of Paclitaxel by endophytic fungi is highly considered as an alternative promising source, but its yield is usually very low in comparison with other taxoids. Different strategies i.e., chemical and physical elicitations have been developed in order to overcome the shortage of Paclitaxel production. Paclitaxel biosynthesis is started with terpenoid pathway followed by phenylpropanoid metabolism where a benzoylphenylisoserine moiety is attached to C13 of baccatin III skeleton. This point which is catalyzed by the function of PAM seems to be a bottleneck that limits the rate of Paclitaxel production. Whether phenylpropanoids pathway regulates the taxanes biosynthesis in Cryptosporiopsis tarraconensis endophytic fungus elicited with benzoic acid (BA) was hypothesized in the present paper. The involvement of certain signal molecules and key enzymes of terpenoid and phenylpropanoid metabolism were investigated. According to the results, application of BA promoted a signaling pathway which was started with increase of H2O2 and ABA and continued by increase of NO and MJ, and finally resulted in increase of both phenylpropanoids and taxanes. However, again the rate of Paclitaxel production was lower than other taxoids, and the latter was much lower than phenolics. Therefore, supplying benzoic acid provided the precursor for the common taxan ring production. It is unlikely that Paclitaxel production is merely controlled by side chain production stage. It is more likely that in C. tarraconensis endophytic fungus, similar to Taxus sp., the competition between phenylpropanoid and taxoid pathways for substrate ended in favor of the former. The interaction network which was constructed based on DSPC algorithm confirmed that most compounds with close proximity have shared metabolic pathway relationships. Therefore, it is unlikely that the feeding with a given precursor directly result in increase of a desired metabolite which is composed of different merits.

Insights into Taxol® biosynthesis by endophytic fungi

“…Furthermore, BAPT genes from F. avenaceum and F. tricinctum were found to be highly homologous with those in Taxus plants (KF010843.1; KF010842.1). Interestingly, phenylalanine aminomutase (PAM) from Cryptosporiopsis tarraconensis was identified as a bottleneck and rate-limiting enzyme (Ballakuti and Ghanati 2023 ).…”

“…induced phenylpropanoid metabolism which regulates Taxol biosynthesis (Li et al 1998b ). A recent study shows that PAL enzyme activity was induced with benzoic acid as an elicitor in the endophytic fungus Cryptosporiopsis tarraconensis (Ballakuti and Ghanati 2023 ). The aminomutase catalyzes the transformation of α-phenylalanine into β-phenylalanine, which is further transformed into phenylazirine and followed by hydroxylating at the C2 site (Zhao et al 2016 ).…”

“…Based on the inhibition of DXR (non-MVA pathway), fungi may require the DXR enzyme to form a MEP pathway similar to plants and bacteria. Further evidence comes from methyl jasmonate and benzoic acid treated fungal cultures of C. tarraconensis showing increased DXR enzyme activity and production of DAB and baccatin III (Ballakuti and Ghanati 2023 ). In Taxol producing fungi, the presence of precursors such as acetate and phenylalanine increased sterol biosynthesis, while tebuconazole and triadimefon inhibited sterol biosynthesis (Li et al 1998a ; El-Sayed et al 2019a , b ).…”