Journal of Guangxi Normal University(Natural Science Edition) ›› 2026, Vol. 44 ›› Issue (2): 199-210.doi: 10.16088/j.issn.1001-6600.2025022401

• Chemistry and Materials Science • Previous Articles     Next Articles

Secondary Metabolites and Antifungal Activity ofAscidian-Derived Fungus Penicillium sp.

JIA Hui1,2, LU Xinghong1,2, LÜ Dongyan1,2, LIANG Jiaping1,2, XU Weifeng1,2*   

  1. 1. School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin Guangxi 541004, China;
    2. State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University), Guilin Guangxi 541004, China
  • Received:2025-02-24 Revised:2025-05-21 Published:2026-02-03

PDF (PC)

1

Abstract: In this study, the ascidian-derived fungus Penicillium sp. HQ2-12 was investigated to explore the chemical diversity of its secondary metabolites and their antifungal activity against Diaporthe citri. The fungus was cultured on the solid medium of 0.9% sea salt rice for fermentation. Comprehensive techniques, including normal-phase and reverse-phase column chromatography, as well as semi-preparative high-performance liquid chromatography (HPLC), were employed for the isolation, extraction, and purification of secondary metabolites. The structures of the compounds were elucidated using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Antifungal activity was evaluated using the microdilution broth method. A total of 16 known compounds were isolated,including five indole diterpenoids, namely rhizovarin A (1)、rhizovarin B (2)、19-hydroxypenitrem A (3)、PC-M4 (4)、10β-hydroxy-13-desoxypaxilline (5), three quinoline derivatives, namely viridicatol (6)、3-hydroxy-4-phenylquinolin-2(1H)-one (7)、aflaquinolone F (8), seven benzodiazepines, namely arctosin (9)、cyclopenin (10)、(3S)-1,4-benzodiazepine 2,5-dione (11)、(Z)-3-benzylidene-4-methyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (12)、7-methoxycyclopenin (13)、7-methoxycyclopeptin (14)、7-methoxydehydrocyclopeptin (15), and one sterol, namely ergosterol (16).Notably, compounds 1, 2, and 8 represent the first reported isolates from the Penicillium genus. Antifungal activity assays revealed that compounds 1-3 exhibited significant inhibitory activity against D. citri, with minimum inhibitory concentrations (MICs) of 64, 32 and 64 mg/L, respectively. Moreover, compound 6 exhibited significant inhibitory activity against multiple bacterial strains. This study was the first to report the antifungal activity of indole-diterpenoid compounds against D. citri, with compound 2 demonstrating strong antimicrobial activity and potential for further development and research.

Key words: ascidian-derived fungi, secondary metabolites, Diaporthe citri, antifungal activity, antibacterial activity

CLC Number:  O629.9;TQ450
[1] ZHOU Z H, LU S, LIU T T, et al.Biocontrol of Citrus melanose Diaporthe citri by Bacillus subtilis M23[J].Biological Control, 2024, 197:105608.DOI:10.1016/j.biocontrol.2024.105608.
[2] LIU X Y, CHAISIRI C, LIN Y, et al.Effective management of Citrus melanose based on combination of ecofriendly chemicals[J].Plant Disease, 2023, 107(4):1172-1176.DOI:10.1094/PDIS-03-22-0513-RE.
[3] CHAISIRI C, LIU X Y, LIN Y, et al.Diaporthe citri:a fungal pathogen causing melanose disease[J].Plants, 2022, 11(12):1600.DOI:10.3390/plants11121600.
[4] 韦坚芬, 邓志勇, 邓业成, 等.草珊瑚内生真菌SgG4抗植物病原真菌的活性物质研究[J].广西师范大学学报(自然科学版), 2024, 42(2):175-182.DOI:10.16088/j.issn.1001-6600.2023041801.
[5] CHEN J, XU L, ZHANG X Q, et al.Discovery of a natural small-molecule AMP-activated kinase activator that alleviates nonalcoholic steatohepatitis[J].Marine Life Science & Technology, 2023, 5(2):196-210.DOI:10.1007/s42995-023-00168-z.
[6] 李奇聪, 陈洁萍, 欧艳绍, 等.柑橘内生真菌LJZ-Y-11次生代谢产物抑菌活性研究[J].广西师范大学学报(自然科学版), 2023, 41(1):155-163.DOI:10.16088/j.issn.1001-6600.2021102801.
[7] 徐伟锋, 姚飞华, 梁学锋, 等.广豆根内生真菌GDG-180代谢产物研究[J].广西师范大学学报(自然科学版), 2017, 35(1):58-61.DOI:10.16088/j.issn.1001-6600.2017.01.010.
[9] CANTRELL C L, DAYAN F E, DUKE S O.Natural products as sources for new pesticides[J].Journal of Natural Products, 2012, 75(6):1231-1242.DOI:10.1021/np300024u.
[10] 傅春青, 梁春祥, 梁莉芬, 等.嗜盐真菌Cladosporium cladosporioides GXIMD 00533次级代谢产物及其生物活性研究[J].广西师范大学学报(自然科学版), 2025, 43(2):247-257.DOI:10.16088/j.issn.1001-6600.2024082203.
[11] MARRONE P G.Pesticidal natural products-status and future potential[J].Pest Management Science, 2019, 75(9):2325-2340.DOI:10.1002/ps.5433.
[12] 吴信, 刘涛, 陈新.天然产物资源的创新发展[J].中国科学(生命科学), 2025, 55(4):593-595.DOI:10.1360/SSV-2025-0074.
[13] 寸靖芳, 任广伟, 徐蓬军, 等.具有农用活性海洋真菌菌株的筛选和鉴定[J].四川农业科技, 2024(7):128-131.DOI:10.3969/j.issn.1004-1028.2024.07.034.
[14] 李鹏杰, 曹西珍, 顾玉诚, 等.海洋天然药物研究进展系列一:海洋天然产物在抗疟药物研发中的机遇与挑战[J].中国海洋药物, 2025, 44(2):65-80.DOI:10.13400/j.cnki.cjmd.2025.02.007.
[15] 张颖, 张诗, 宁耀东, 等.具有抗真菌活性的海洋天然产物研究进展[J].中国抗生素杂志, 2023, 48(4):361-367.DOI:10.3969/j.issn.1001-8689.2023.04.001.
[16] 姜明华, 陈森华, 郭珩, 等.海鞘微生物来源活性次级代谢产物研究进展[J].中国海洋药物, 2023, 42(3):69-81.DOI:10.13400/j.cnki.cjmd.2023.03.005.
[17] RAMESH C, TULASI B R, RAJU M, et al.Marine natural products from tunicates and their associated microbes[J].Marine Drugs, 2021, 19(6):308.DOI:10.3390/md19060308.
[18] ZOU G, YANG W C, CHEN T, et al.Griseofulvin enantiomers and bromine-containing griseofulvin derivatives with antifungal activity produced by the mangrove endophytic fungus Nigrospora sp.QQYB1[J].Marine Life Science & Technology, 2024, 6(1):102-114.DOI:10.1007/s42995-023-00210-0.
[19] LIU Y F, DU H F, ZHANG Y H, et al.Chaeglobol A, an unusual octocyclic sterol with antifungal activity from the marine-derived fungus Chaetomium globosum HBU-45[J].Chinese Chemical Letters, 2025, 36(3):109858.DOI:10.1016/j.cclet.2024.109858.
[20] DU H F, LI L, ZHANG Y H, et al.The first dimeric indole-diterpenoids from a marine-derived Penicillium sp.fungus and their potential for anti-obesity drugs[J].Marine Life Science & Technology, 2025, 7(1):120-131.DOI:10.1007/s42995-024-00253-x.
[21] SHIN H J.Natural products from marine fungi[J].Marine Drugs, 2020, 18(5):230.DOI:10.3390/md18050230.
[22] CARROLL A R, COPP B R, GRKOVIC T, et al.Marine natural products[J].Natural Product Reports, 2025, 42(2):257-297.DOI:10.1039/d4np00067f.
[23] MA H G, LIU Q, ZHU G L, et al.Marine natural products sourced from marine-derived Penicillium fungi[J].Journal of Asian Natural Products Research, 2016, 18(1):92-115.DOI:10.1080/10286020.2015.1127230.
[24] BARRETO D L C, LOWELL CANTRELL C, KARLA DA SILVA M, et al.Phytotoxic and antifungal activity of (-)-penienone produced by Penicillium palitans (ascomycota) isolated from deep sea sediments in the southern ocean, maritime Antarctica[J].Chemistry & Biodiversity, 2025, 22(3):e202401603.DOI:10.1002/cbdv.202401603.
[25] VIEIRA G, SETTE L D, DE ANGELIS D A, et al.Antifungal activity of cyclopaldic acid from Antarctic Penicillium against phytopathogenic fungi[J].3 Biotech, 2023, 13(11):374.DOI:10.1007/s13205-023-03792-9.
[26] HAN Y Q, ZHANG Q, XU W F, et al.Targeted isolation of antitubercular cycloheptapeptides and an unusual pyrroloindoline-containing new analog, asperpyrroindotide A, using LC-MS/MS-based molecular networking[J].Marine Life Science & Technology, 2023, 5(1):85-93.DOI:10.1007/s42995-022-00157-8.
[27] ZHOU J T, WU Q, ZHAO J X, et al.Sucurchalasins a and B, sulfur-containing heterodimers of a cytochalasan and a macrolide from the endophytic fungus Aspergillus spelaeus GDGJ-286[J].Journal of Natural Products, 2024, 87(9):2327-2334.DOI:10.1021/acs.jnatprod.4c00489.
[28] PENG Z H, JIA H, LUO Y L, et al.Talaroterpenoids A-F:six new seco-terpenoids from the marine-derived fungus Talaromyces aurantiacus[J].Marine Drugs, 2024, 22(10):475.DOI:10.3390/md22100475.
[29] ZHOU T Y, GUO Y Y, JING Q Q, et al.Semisynthesis and biological evaluation of 17-hydroxybrevianamide N derivatives as anti-inflammatory agents by mediating NF-κB and MAPK signaling pathways[J].European Journal of Medicinal Chemistry, 2025, 290:117541.DOI:10.1016/j.ejmech.2025.117541.
[30] MO T X, LV L X, HUANG X S, et al.A series of meroterpenoids with highly oxygenated skeletons from the endophytic fungus Penicillium sp.and their anti-inflammatory activities[J].Phytochemistry, 2025, 236:114493.DOI:10.1016/j.phytochem.2025.114493.
[31] XIE Y H, WANG C H, WANG R, et al.Anti-neuroinflammatory naphthol dimers from the marine-derived fungus Penicillium sp.HQ1-23[J].Phytochemistry, 2025, 237:114534.DOI:10.1016/j.phytochem.2025.114534.
[32] 邓欢, 王玉军.杀菌剂百菌清的研究进展[J].轻工科技, 2012, 28(4):26-27.
[33] GAO S S, LI X M, WILLIAMS K, et al.Rhizovarins A-F, indole-diterpenes from the mangrove-derived endophytic fungus Mucor irregularis QEN-189[J].Journal of Natural Products, 2016, 79(8):2066-2074.DOI:10.1021/acs.jnatprod.6b00403.
[34] ZHANG P, LI X M, LI X, et al.New indole-diterpenoids from the algal-associated fungus Aspergillus nidulans[J].Phytochemistry Letters, 2015, 12:182-185.DOI:10.1016/j.phytol.2015.03.017.
[35] YAMAGUCHI T, NOZAWA K, HOSOE T, et al.Indoloditerpenes related to tremorgenic mycotoxins, penitrems, from Penicillium crustosum[J].Phytochemistry, 1993, 32(5):1177-1181.DOI:10.1016/S0031-9422(00)95087-8.
[36] HOSOE T, NOZAWA K, UDAGAWA S I, et al.Studies on fungal products.Part XXXIII.Structures of new indoloditerpenes, possible biosynthetic precursors of the tremorgenic mycotoxins, penitrems, from Penicillium crustosum[J].Chemical and Pharmaceutical Bulletin, 1990, 38(12):3473-3475.DOI:10.1248/cpb.38.3473.
[37] ZHANG Y H, HUANG S D, PAN H Q, et al.Structure determination of two new indole-diterpenoids from Penicillium sp.CM-7 by NMR spectroscopy[J].Magnetic Resonance in Chemistry, 2014, 52(6):306-309.DOI:10.1002/mrc.4065.
[38] 冯丹, 秦玲玲, 郑东滨, 等.冬虫夏草内生菌皮壳青霉菌化学成分的研究[J].中成药, 2019, 41(8):1863-1867.DOI:10.3969/j.issn.1001-1528.2019.08.022.
[39] NEFF S A, LEE S, ASAMI Y, et al.Aflaquinolones A-G:secondary metabolites from marine and fungicolous isolates of Aspergillus spp[J].Journal of Natural Products, 2012, 75(3):464-472.DOI:10.1021/np200958r.
[40] 刘军亮, 楼盈凯, 胡志钰, 等.圆弧菌醇和圆弧菌素的分离纯化及结构解析[J].厦门大学学报(自然科学版), 2012, 51(3):386-390.
[41] 辛志宏, 方玉春, 朱天骄, 等.海绵来源真菌黄灰青霉Sp-19中的抗肿瘤活性成分研究[J].中国海洋药物, 2006, 25(6):1-6.DOI:10.3969/j.issn.1002-3461.2006.06.002.
[42] PAN C Q, SHI Y T, CHEN X G, et al.New compounds from a hydrothermal vent crab-associated fungus Aspergillus versicolor XZ-4[J].Organic & Biomolecular Chemistry, 2017, 15(5):1155-1163.DOI:10.1039/C6OB02374F.
[43] 盛蒙珂, 赵莹菲, 田若丹, 等.怀山药内生真菌Chaetomium sp.的次生代谢产物研究[J].天然产物研究与开发, 2024, 36(6):982-985, 962.DOI:10.16333/j.1001-6880.2024.6.008.
[44] FU P N, GUO F, ZHOU T N, et al.Shearinines U-Y, indole diterpenoids from an entomogenous fungus, Penicillium sp[J].RSC Advances, 2025, 15(4):2437-2443.DOI:10.1039/D4RA08249D.
[45] KALININA S A, JAGELS A, CRAMER B, et al.Influence of environmental factors on the production of penitrems A-F by Penicillium crustosum[J].Toxins, 2017, 9(7):210.DOI:10.3390/toxins9070210.
[46] BABU J, POPAY A J, MILES C O, et al.Identification and structure elucidation of janthitrems a and D from Penicillium janthinellum and determination of the tremorgenic and anti-insect activity of janthitrems a and B[J].Journal of Agricultural and Food Chemistry, 2018, 66(50):13116-13125.DOI:10.1021/acs.jafc.8b04964.
[47] LIANG J H, HUO X K, CHENG Z B, et al.An indole diterpenoid isolated from the fungus Drechmeria sp.and its antimicrobial activity[J].Natural Product Research, 2019, 33(19):2770-2776.DOI:10.1080/14786419.2018.1501050.
[48] LIANG Z Y, SHEN N X, ZHOU X J, et al.Bioactive indole diterpenoids and polyketides from the marine-derived fungus Penicillium javanicum[J].Chemistry of Natural Compounds, 2020, 56(2):379-382.DOI:10.1007/s10600-020-03039-6.
[49] PANG S, GUO Z G, WANG L, et al.Anti-IAV indole-diterpenoids from the marine-derived fungus Penicillium citrinum[J].Natural Product Research, 2023, 37(4):586-591.DOI:10.1080/14786419.2022.2078820.
[50] 刘胜贵, 周玉莎, 易江, 等.柑橘内生菌的分离、鉴定及其对沙皮病的防治作用[J].生命科学研究, 2016, 20(5):429-434.DOI:10.16605/j.cnki.1007-7847.2016.05.010.
[51] 谢钢, 裴皓然, 张家辉, 等.生防菌QD15的筛选鉴定及对柑橘砂皮病防治初步研究[J].湖南农业科学, 2024(4):60-66.DOI:10.16498/j.cnki.hnnykx.2024.004.012.
[1] CHEN Xueyu, SHI Huilu, HUANG Qiuju, BIAN Xun, LUO Haiyu. Isolation and Identification of Intestinal Bacteria from Callimenellus fumidus Walker and Screening of Antifung Active Strains [J]. Journal of Guangxi Normal University(Natural Science Edition), 2025, 43(6): 204-214.
[2] XU Ziwei, DENG Yecheng, LUO Haiyu, DENG Zhiyong, WEI Jianfen, HUANG Lingyu, GAN Pinggui. Study on the Antifungal Activity of Secondary Metabolites from Active Endophytic Fungi Isolated from Paederia scandens (Lour.) Merr. [J]. Journal of Guangxi Normal University(Natural Science Edition), 2025, 43(1): 31-38.
[3] WEI Jianfen, DENG Zhiyong, DENG Yecheng, LUO Haiyu, MENG Siyu, XU Ziwei, SHI Yao, LIANG Wenken. Study on the Active Substances of Endophytic Fungus SgG4 from Sarcandra glabra Against Plant Pathogenic Fungi [J]. Journal of Guangxi Normal University(Natural Science Edition), 2024, 42(2): 175-182.
[4] XIAO Ze'en, ZOU Sihua, JIANG Jiao, LUO Haimei, HUANG Xishan, LIU Yonghong, TAN Zhen. Secondary Metabolites and Its Hypoglycemic of Endophytic Fungus Penicillium sp. GXIMD00006 Derived from the Bruguiera gymnorrhiza [J]. Journal of Guangxi Normal University(Natural Science Edition), 2023, 41(6): 150-157.
[5] DU Libo, LI Jinyu, ZHANG Xiao, LI Yonghong, PAN Weidong. Chemical Constituents and Biological Activity from the Bark of Toona ciliata var. pubescens [J]. Journal of Guangxi Normal University(Natural Science Edition), 2022, 40(4): 162-172.
[6] HUANG Wanyun , YIN Penglong , LI Hong , PENG Xiangyan , SU Guifa. Synthesis and Antitumor, Antibacterial ActivityEvaluation of Ferrocene-quinolone Hybrids [J]. Journal of Guangxi Normal University(Natural Science Edition), 2016, 34(2): 111-115.
[7] LIU Han-fu, MA Xian-li, CHEN Su-yi , SHEN Xue-song, HUANG Fu-ping. Synthesis and Antibacterial Activity of Ternary Zinc Complex [J]. Journal of Guangxi Normal University(Natural Science Edition), 2015, 33(4): 103-107.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] TIAN Sheng, ZHAO Kailong, MIAO Jialin. Research on Automatic Driving Road Traffic Detection Algorithm Based on Improved YOLO11n Model[J]. Journal of Guangxi Normal University(Natural Science Edition), 2026, 44(1): 1 -9 .
[2] XU Xiuhong, ZHANG Jinyan, LU Yuling, LIANG Xiaoping, LIAO Guangfeng, LU Rumei. Research Progress of New C21 Steroids in Medicinal Plants of Asclepiadaceae(Ⅱ)[J]. Journal of Guangxi Normal University(Natural Science Edition), 2026, 44(2): 1 -16 .
[3] WANG Xingyu, ZHENG Haonan, LIU Xiao, CUI Shilong, CAI Jinjun. Research Progress on Preparation of Chitosan-based Adsorbents andTheir Applications Towards Adsorptive Removal of Pollutants From Water[J]. Journal of Guangxi Normal University(Natural Science Edition), 2026, 44(2): 17 -30 .
[4] TIAN Sheng, FENG Shuaitao, LI Jia. A Framework for Enhanced Vehicle Trajectory Extraction in Urban Road Scenes[J]. Journal of Guangxi Normal University(Natural Science Edition), 2026, 44(2): 31 -51 .
[5] LÜ Hui, SI Ke. Photovoltaic Panel Defect Detection Based on Improved RT-DETR[J]. Journal of Guangxi Normal University(Natural Science Edition), 2026, 44(2): 52 -64 .
[6] SONG Guanwu, LI Jianjun. Semantic Segmentation of Remote Sensing Images Basedon Self-distillation Edge Refinement[J]. Journal of Guangxi Normal University(Natural Science Edition), 2026, 44(2): 65 -76 .
[7] WANG Xuyang, LIANG Yuhang. Multi-scale Asymmetric Attention Transformer for Remote Sensing Image Dehazing[J]. Journal of Guangxi Normal University(Natural Science Edition), 2026, 44(2): 77 -89 .
[8] ZHANG Shengwei, CAO Jie. Detection Algorithm of Tiny Defects on Steel Surface Based onFourier Convolution and Difference Perception[J]. Journal of Guangxi Normal University(Natural Science Edition), 2026, 44(2): 90 -102 .
[9] WANG Wei, LI Zhiwei, ZHANG Zhaoyang, ZHANG Hong, ZHOU Li, WANG Zhen, HUANG Fang, WANG Can. Carbon Emission Prediction of Substation Based on IFA-BP Neural Network Model[J]. Journal of Guangxi Normal University(Natural Science Edition), 2026, 44(2): 103 -114 .
[10] LUO Yuan, ZHU Wenzhong, WANG Wen, WU Yuhao. A Multi-step Water Quality Prediction Model Based on Improved PatchTST[J]. Journal of Guangxi Normal University(Natural Science Edition), 2026, 44(2): 115 -131 .
Copyright © Journal of Guangxi Normal University(Natural Science Edition), All Rights Reserved.
Tel: 0773-5857325　E-mail: gxsdzkb@mailbox.gxnu.edu.cn
Powered by Beijing Magtech Co. Ltd