**Stress-Induced Mucus Secretion and Its Composition by a Combination of Proteomics and Metabolomics of the Jellyfish** *Aurelia coerulea*

**Wenwen Liu 1,2,†, Fengfeng Mo 3,†, Guixian Jiang 4,†, Hongyu Liang 1,2, Chaoqun Ma 2, Tong Li 5, Lulu Zhang 2, Liyan Xiong 6, Gian Luigi Mariottini 7, Jing Zhang 1,\* and Liang Xiao 2,\***


Received: 24 August 2018; Accepted: 9 September 2018; Published: 18 September 2018

**Abstract:** Background: Jellyfish respond quickly to external stress that stimulates mucus secretion as a defense. Neither the composition of secreted mucus nor the process of secretion are well understood. Methods: *Aurelia coerulea* jellyfish were stimulated by removing them from environmental seawater. Secreted mucus and tissue samples were then collected within 60 min, and analyzed by a combination of proteomics and metabolomics using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), respectively. Results: Two phases of sample collection displayed a quick decrease in volume, followed by a gradual increase. A total of 2421 and 1208 proteins were identified in tissue homogenate and secreted mucus, respectively. Gene Ontology (GO) analysis showed that the mucus-enriched proteins are mainly located in extracellular or membrane-associated regions, while the tissue-enriched proteins are distributed throughout intracellular compartments. Tryptamine, among 16 different metabolites, increased with the largest-fold change value of 7.8 in mucus, which is consistent with its involvement in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway 'tryptophan metabolism'. We identified 11 metalloproteinases, four serpins, three superoxide dismutases and three complements, and their presence was speculated to be related to self-protective defense. Conclusions: Our results provide a composition profile of proteins and metabolites in stress-induced mucus and tissue homogenate of *A. coerulea.* This provides insight for the ongoing endeavors to discover novel bioactive compounds. The large increase of tryptamine in mucus may indicate a strong stress response when jellyfish were taken out of seawater and the active self-protective components such as enzymes, serpins and complements potentially play a key role in innate immunity of jellyfish.

**Keywords:** jellyfish; *Aurelia coerulea*; mucus; proteomics; metabolomics
