Solving the Jigsaw puzzle of phytosterol diversity by a novel sterol methyltransferase from Zea mays

Phytosterols are vital structural and regulatory components in plants. Zea mays produces a series of phytosterols that are specific to corn. However, the underline biosynthetic mechanism remains elusive. In this study, we identified a novel sterol methyltransferase from Z. mays (ZmSMT1–2) which showed a unique feature compared with documented plant SMTs. ZmSMT1–2 showed a substrate preference for cycloartenol. Using S-adenosyl-L-methionine (AdoMet) as a donor, ZmSMT1–2 converted cycloartenol into alkylated sterols with unique side-chain architectures, including Δ²⁵⁽²⁷⁾ (i.e., cyclolaudenol and cycloneolitsol) and Δ²⁴⁽²⁵⁾ (i.e., cyclobranol) sterols. Cycloneolitsol is identified as a product of SMTs for the first time. Our discovery provides a previously untapped mechanism for phytosterol biosynthesis and adds another layer of diversity of sterol biosynthesis.