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               Cembrane-type  diterpenoids  in  soft  coral  Sclerophytum  flexibile  and  the

               impact of changes in its associated microbiome


                                                    2,3
                                                                      4,5
                                                                                     2
               Li-Guo Zheng,  #,1,2  Wei-Zhong Chen,  You-Ying Chen,  Jimmy Kuo,  Ping-Jyun Sung,*
                                                                                                         ,2
               Jui-Hsin Su* ,2

               1  Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University,
                 Kaohsiung 804201, Taiwan
               2  National Museum of Marine Biology and Aquarium, Pingtung 944401, Taiwan
               3  Graduate  Institute of  Marine Biology, National  Dong Hwa University,  Pingtung  944401,
                 Taiwan
               4  Xiamen Key Laboratory of Natural Products Resources of Marine Medicine, Xiamen
                 Medical College, Xiamen 361023, China
               5  Fujian Provincial University Marine Biomedical Resources Engineering Research Center,
                 Xiamen Medical College, Xiamen 361023, China
               * E-mail: pjsung@nmmba.gov.tw;   x2219@nmmba.gov.tw

               Abstract
                  The soft coral Sclerophytum flexibile contains one of the most promising marine natural
               products: cembrane-type diterpenoids. Numerous studies have indicated that these cembranoids
               exhibit a variety of biological activities, including significant anti-inflammatory effects. Since
               2016, we have been sustainably cultivating S. flexibile using aquaculture techniques to produce
               these valuable bioactive compounds while protecting natural habitats. However, in 2022, we
               observed that the levels of active cembranoids gradually decreased in cultured corals over time.
               To investigate this problem, we used liquid chromatography–tandem mass spectrometry (LC-
               MS/MS) to analyze the cembranoid content of both wild and cultured corals. We identified that
               bioactive cembrane-type diterpenoids were maintained at high levels in wild S. flexibile. In
               addition, we found significant differences in the coral microbiome composition between wild
               and cultured corals by using next-generation sequencing (NGS). Wild corals were enriched with
               Proteobacteria and Spirochaetes, while cultured corals had relatively higher levels of Firmicutes
               and Bacteroidetes. Differences were also revealed at the bacterial family level. In conclusion,
               the bacterial communities of wild and cultured corals differ greatly. These findings suggest that
               changes in the coral microbiome may lead to reduced production of bioactive compounds in
               cultured corals.




















               Keywords: Sclerophytum flexibile; Soft coral; Cembranoids; Associated Microbiome
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