Tylosin (TYN) is widely used in veterinary prophylactic as a macrolide and frequently detected in the surface water. Previous studies showed that exposure to TYN caused suppression of chlorophyll biosynthesis and inhibition of photosynthesis at the physiological level, associated with reduced growth performances in algae, but the molecular mechanisms remain unknown, especially at environmental exposure levels. The present study elucidated the underlying molecular mechanism(s) of TYN toxicity in a model green alga Raphidocelis subcapitata using approaches of transcriptomics and metabolomics. Following a 7-day exposure, algal growth performances were reduced by 26.3% and 58.3% in the 3 (an environmentally realistic level) and 400 μg L⁻¹ TYN treatment group, respectively. A total of 577 (99) and 5438 (180) differentially expressed genes (differentially accumulated metabolites) were identified in algae treated with 3 and 400 μg L⁻¹ TYN, respectively. Signaling pathways including photosynthesis – antenna protein, porphyrin and chlorophyll metabolism, carbon fixation in photosynthetic organisms, and DNA replication were altered in the 400 μg L⁻¹ TYN treatment, while photosynthesis and DNA replication were the shared pathways in both TYN treatments. The metabolomic data further suggest that molecular pathways related to photosynthesis, DNA replication-coupled repair and energy metabolism were impaired. Photosynthesis was identified as the most sensitive target of TYN toxicity in R. subcapitata, in contrast to protein synthesis inhibition caused by TYN in bacteria. This study provides novel mechanistic information of TYN toxicity in R. subcapitata.

泰乐菌素 (TYN) 作为大环内酯广泛用于兽医预防，并且经常在地表水中检测到。先前的研究表明，暴露于 TYN 会在生理水平上抑制叶绿素生物合成和光合作用，这与藻类的生长性能降低有关，但分子机制仍然未知，尤其是在环境暴露水平下。本研究使用转录组学和代谢组学方法阐明了模型绿藻Raphidocelis subcapitata中 TYN 毒性的潜在分子机制。暴露 7 天后，3（环境现实水平）和 400 μg L ^{-1 的}藻类生长性能分别降低了 26.3% 和 58.3%TYN 治疗组。在分别用 3 和 400 μg L ^-1 TYN处理的藻类中，总共鉴定出 577 (99) 和 5438 (180) 个差异表达基因（差异积累的代谢物）。信号通路包括光合作用 - 天线蛋白、卟啉和叶绿素代谢、光合生物中的碳固定和 DNA 复制在 400 μg L ^-1 TYN 处理中发生改变，而光合作用和 DNA 复制是两种 TYN 处理的共享通路。代谢组学数据进一步表明，与光合作用、DNA 复制偶联修复和能量代谢相关的分子途径受损。光合作用被确定为R. subcapitata TYN 毒性最敏感的目标，与细菌中 TYN 引起的蛋白质合成抑制相反。这项研究提供了R. subcapitata中 TYN 毒性的新机制信息。