Abstract
Diosgenin serves as an important precursor of most steroidal drugs in market. Cholesterol was previously deemed as a sterol origin leading to diosgenin biosynthesis. This study reports that cholesterol is not in parallel with diosgenin biosynthesis in Trigonella foenum-graecum. We first perturbed its sterol composition using inhibitors specific for the upstream isoprenoid pathway enzymes, HMGR (3-hydroxy-3-methylgutaryl-CoA reductase) on the mevalonate (MVA) and DXR (1-deoxy-D-xylulose-5-phosphate reductoisomerase) on the 2-C-methyl-D-erythritol-4-phophate (MEP) pathways, and have revealed that diosgenin and cholesterol reversely or differently accumulated in either the MVA or the MEP pathway-suppressed plants, challenging the previously proposed role of cholesterol in diosgenin biosynthesis. To further investigate this, we altered the sterol composition by suppressing and overexpressing the 24-sterol methyltransferase type 1 (SMT1) gene in T. foenum-graecum, as SMT1 acts in the first committed step of diverting the carbon flux of cholesterol toward biosynthesis of 24-alkyl sterols. Knockdown of TfSMT1 expression led to increased cholesterol level but caused a large reduction of diosgenin. Diosgenin was increased upon the TfSMT1-overexpressing, which, however, did not significantly affect cholesterol biosynthesis. These data consistently supported that diosgenin biosynthesis in T. foenum-graecum is not associated with cholesterol. Rather, campesterol, a 24-alkyl sterol, was indicative of being correlative to diosgenin biosynthesis in T. foenum-graecum.
Highlights
Trigonella foenum-graecum, named fenugreek, originates from the Iran and Mediterranean regions (Mostafaie et al, 2018)
Two-day-old T. foenum-graecum seedlings were subjected to the Lov- and Fos-treatments for different time lengths, and the treated seedlings were analyzed for altered diosgenin level and sterol composition
Fosmidomycin generally increased the diosgenin production to different extents over the controls at most of the time points, with the exception of a decrease of diosgenin observed at the 72 h and no significant changes seen at the 144 h (Figure 2C)
Summary
Trigonella foenum-graecum, named fenugreek, originates from the Iran and Mediterranean regions (Mostafaie et al, 2018). In an intact animal mode, diosgenin was shown to inhibit the growth of rat colon tumor (Raju et al, 2004), human breast cancer (Srinivasan et al, 2009), and lung adenocarcinoma tumors (Yan et al, 2009). Those studies raise the prospect of developing diosgenin as a natural product-based antitumor drug. In contrast with the intense interests on its pharmacological activities, knowledge about the diosgenin biosynthetic pathway is much less established
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