Sorbicillinoids From the Fungus Ustilaginoidea virens and Their Phytotoxic, Cytotoxic, and Antimicrobial Activities

Abstract

<i>Ustilaginoidea virens</i>, the causal fungus of rice false smut, was found in previous studies to produce two types of metabolites, ustiloxins and ustilaginoidins. However, genome sequencing of <i>U. virens</i> revealed a plethora of secondary-metabolites-biosynthetic core genes that were capable to biosynthesize unreported metabolites. A large-scale fermentation of <i>U. virens</i> was thus performed, and the fungal extract was chemically re-investigated. After removing the known metabolites, we found a fraction containing unknown phytotoxic substances. Fractionation of this part has led to the isolation of six new sorbicillinoids, namely ustisorbicillinols A~F (<b>1</b>~<b>6</b>), and two new sorbicillinoid-related pyrones, named ustilopyrones A (<b>7</b>) and B (<b>8</b>), together with nine known cogeners (<b>9</b>~<b>17</b>). The structures of the new compounds were elucidated by analysis of their NMR, HRMS, and CD spectra, while ECD, ¹³C NMR and optical rotation calculations were additionally used for configurational assignments. Plausible biosynthetic pathways for the new compounds were proposed. Phytotoxicity assays revealed that the major sorbicillinoids (<b>12</b>~<b>14</b>, and <b>16</b>) showed strong inhibition against the radicle and germ elongation of rice and lettuce seeds, with compound <b>12</b> displaying the strongest inhibition. The isolated compounds were also evaluated for their cytotoxic, antibacterial, and antifungal activities. Compounds <b>10</b>, and <b>12</b>~<b>14</b> showed moderate cytotoxicities against the tested cell lines with IC₅₀s of 8.83~74.7 μM. Compounds <b>2</b>, and <b>10</b>~<b>13</b> were active against the tested bacteria (MICs 4~128 μg/mL), while compounds <b>11</b>~<b>13</b> displayed moderate antifungal activities.