TY - JOUR
T1 - Tricarballylic ester formation during biosynthesis of fumonisin mycotoxins in Fusarium verticillioides
AU - Li, Yaoyao
AU - Lou, Lili
AU - Cerny, Ronald L.
AU - Butchko, Robert A.E.
AU - Proctor, Robert H.
AU - Shen, Yuemao
AU - Du, Liangcheng
N1 - Funding Information:
This work was supported in part by National Natural Science Foundation of China [grant number 31329005] and National Science Foundation [grant number MCB-0614916].
PY - 2013/12
Y1 - 2013/12
N2 - Fumonisins are agriculturally important mycotoxins produced by the maize pathogen Fusarium verticillioides. The chemical structure of fumonisins contains two tricarballylic esters, which are rare structural moieties and important for toxicity. The mechanism for the tricarballylic ester formation is not well understood. FUM7 gene of F. verticillioides was predicted to encode a dehydrogenase/reductase, and when it was deleted, the mutant produced tetradehydro fumonisins (DH4-FB). MS and NMR analysis of DH4-FB1 indicated that the esters consist of aconitate with a 3′-alkene function, rather than a 2′-alkene function. Interestingly, the purified DH4-FB1 eventually yielded three chromatographic peaks in HPLC. However, MS revealed that the metabolites of the three peaks all had the same mass as the initial single-peak DH4-FB1. The results suggest that DH4-FB1 can undergo spontaneous isomerization, probably including both cis-trans stereoisomerization and 3′- to 2′-ene regioisomerization. In addition, when FUM7 was expressed in Escherichia coli and the resulting enzyme, Fum7p, was incubated with DH4-FB, no fumonisin with typical tricarballylic esters was formed. Instead, new fumonisin analogs that probably contained isocitrate and/or oxalosuccinate esters were formed, which reveals new insight into fumonisin biosynthesis. Together, the data provided both genetic and biochemical evidence for the mechanism of tricarballylic ester formation in fumonisin biosynthesis.
AB - Fumonisins are agriculturally important mycotoxins produced by the maize pathogen Fusarium verticillioides. The chemical structure of fumonisins contains two tricarballylic esters, which are rare structural moieties and important for toxicity. The mechanism for the tricarballylic ester formation is not well understood. FUM7 gene of F. verticillioides was predicted to encode a dehydrogenase/reductase, and when it was deleted, the mutant produced tetradehydro fumonisins (DH4-FB). MS and NMR analysis of DH4-FB1 indicated that the esters consist of aconitate with a 3′-alkene function, rather than a 2′-alkene function. Interestingly, the purified DH4-FB1 eventually yielded three chromatographic peaks in HPLC. However, MS revealed that the metabolites of the three peaks all had the same mass as the initial single-peak DH4-FB1. The results suggest that DH4-FB1 can undergo spontaneous isomerization, probably including both cis-trans stereoisomerization and 3′- to 2′-ene regioisomerization. In addition, when FUM7 was expressed in Escherichia coli and the resulting enzyme, Fum7p, was incubated with DH4-FB, no fumonisin with typical tricarballylic esters was formed. Instead, new fumonisin analogs that probably contained isocitrate and/or oxalosuccinate esters were formed, which reveals new insight into fumonisin biosynthesis. Together, the data provided both genetic and biochemical evidence for the mechanism of tricarballylic ester formation in fumonisin biosynthesis.
KW - Fusarium verticillioides
KW - biosynthesis
KW - fumonisins
KW - mycotoxins
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U2 - 10.1080/21501203.2013.874540
DO - 10.1080/21501203.2013.874540
M3 - Article
C2 - 24587959
AN - SCOPUS:84893758963
VL - 4
SP - 179
EP - 186
JO - Mycology
JF - Mycology
SN - 2150-1203
IS - 4
ER -