Coculture of Coastal Macroalga-Epiphytic <i>Trichoderma</i> Fungi for Microalgal Algicide Production Highlighted by an Iodinated Terpenoid

Macro- and microalgae are primary producers in coastal ecosystems, and the former harbor diverse microbes. During our investigation of the fungi associated with estuarine macroalgae, <i>Trichoderma</i> spp. appeared predominant as epiphytes and exhibited no host affiliation. Furthermore, a dual culture of algicolous <i>T. virens</i> and <i>T. longibrachiatum</i> led to the production of 21 metabolites, including eight new terpenoids (<b>1</b>-<b>3</b>, <b>5</b>-<b>7</b>, <b>11</b>, and <b>12</b>) and three new alkaloids (<b>14</b>, <b>15</b>, and <b>21</b>), identified by combined spectroscopic data. The terpenoids comprise four frameworks, especially the unusual eudesmane (<b>3</b> and <b>4</b>) in <i>Trichoderma</i> and the rare 6/7 fused ring system (<b>11</b>-<b>13</b>) in nature. Compounds <b>1</b>, <b>3</b>, and <b>4</b> feature characteristic halogenations, while <b>14</b> and <b>15</b> represent the first two hydroxylated derivatives at C-3 of gliotoxin. HPLC analysis revealed that <b>1</b>, <b>3</b>, <b>9</b>-<b>12</b>, <b>14</b>-<b>16</b>, and <b>21</b> were induced by the coculture. Among them, iodine-bearing terpenoid <b>3</b> was evaluated as the most broad-spectrum algicide against representative microalgae, which could cause harmful algal blooms. However, it only weakly inhibited the microalgae that can be used as bait in aquaculture and the zooplankton tested. This metabolite may be developed as a promising modulator of coastal microalgal communities.