Progress in the Mining and Utilization of Insect-associated Actinomycete Resources

doi:10.13560/j.cnki.biotech.bull.1985.2024-0298

Abstract

Abstract:

Insects are one of the most species-diverse groups of organisms in nature, and they have established close symbiotic relationships with a variety of functionally unique symbionts during their long evolutionary process. These symbiotic relationships were understood to be mutually beneficial in the early days, and recent studies have also revealed commensalism and parasitism. Among these symbionts, actinomycetes are a special group of microorganisms that can be found in the insect gut, feces, antennae, exoskeleton, and the fungus gardens of fungus-growing insects, which help host insects to defend themselves against pathogens, parasites, and predators, and they play an important role in maintaining the survival and reproduction of host insects. In recent years, a variety of novel compounds have been isolated from the metabolites produced by insect-associated actinomycetes, which can inhibit the proliferation of various plant and animal pathogens, tumor cells, and cancer cells. Therefore, the study on insect-associated actinomycetes can not only analyze the symbiotic mechanism between host and microorganisms but also provide new options for developing biopesticides and biopharmaceuticals. This paper reviews the research progress on the mining and utilization of insect-associated actinomycetes, mainly summarizes the resources and functional diversity of different species of insect-associated actinomycetes, concurrently classifies the secondary metabolites of insect-associated actinomycetes with important activities according to the structural differences, including polypeptide, quinine and polyketide, lactone, alkaloid and other compounds, as well as explores the functional diversity of these secondary metabolites, thus providing a foundation for understanding the operation of ecosystems, discovering new bioactive substances, and developing new biopesticides and pharmaceuticals.

Key words: insects, actinomycetes, secondary metabolites

ZHAO Zheng-yang, XIE Bing-yan, CHENG Xin-yue, LI Hui-xia. Progress in the Mining and Utilization of Insect-associated Actinomycete Resources[J]. Biotechnology Bulletin, 2024, 40(11): 113-124.

Figures/Tables 1

References 126

[1]	Misof B, Liu SL, Meusemann K, et al. Phylogenomics resolves the timing and pattern of insect evolution[J]. Science, 2014, 346(6210): 763-767.
[2]	Basset Y, Cizek L, Cuénoud P, et al. Arthropod diversity in a tropical forest[J]. Science, 2012, 338(6113): 1481-1484.
[3]	Buchner P. Endosymbiose der Tiere mit Pflanzlichen Mikroorganismen[M]. Basel: Birkhäuser Basel, 1953.
[4]	Matarrita-Carranza B, Murillo-Cruz C, Avendaño R, et al. Streptomy-ces sp. M54: an Actinobacteria associated with a neotropical social wasp with high potential for antibiotic production[J]. Antonie Van Leeuwenhoek, 2021, 114(4): 379-398.
[5]	Usman M, Farooq M, Wakeel A, et al. Nanotechnology in agriculture: current status, challenges and future opportunities[J]. Sci Total Environ, 2020, 721: 137778.
[6]	Sheehan G, Garvey A, Croke M, et al. Innate humoral immune defences in mammals and insects: the same, with differences?[J]. Virulence, 2018, 9(1): 1625-1639.
[7]	Van Arnam EB, Currie CR, Clardy J. Defense contracts: molecular protection in insect-microbe symbioses[J]. Chem Soc Rev, 2018, 47(5): 1638-1651.
[8]	Nechitaylo TY, Sandoval-Calderón M, Engl T, et al. Incipient genome erosion and metabolic streamlining for antibiotic production in a defensive symbiont[J]. Proc Natl Acad Sci USA, 2021, 118(17): e2023047118.
[9]	Donald L, Pipite A, Subramani R, et al. Streptomyces: still the biggest producer of new natural secondary metabolites, a current perspective[J]. Microbiol Res, 2022, 13(3): 418-465.
[10]	Genilloud O. Actinomycetes: still a source of novel antibiotics[J]. Nat Prod Rep, 2017, 34(10): 1203-1232.
[11]	Van Moll L, De Smet J, Cos P, et al. Microbial symbionts of insects as a source of new antimicrobials: a review[J]. Crit Rev Microbiol, 2021, 47(5): 562-579.
[12]	Chevrette MG, Carlson CM, Ortega HE, et al. The antimicrobial potential of Streptomyces from insect microbiomes[J]. Nat Commun, 2019, 10(1): 516.
[13]	Poulsen M, Oh DC, Clardy J, et al. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery[J]. PLoS One, 2011, 6(2): e16763.
[14]	Matsui T, Tanaka J, Namihira T, et al. Antibiotics production by an actinomycete isolated from the termite gut[J]. J Basic Microbiol, 2012, 52(6): 731-735.
[15]	尹彩萍, 白雪妍, Naeem ABBAS, 等. 黑翅土白蚁肠道放线菌菌株BYC-18及其抗菌代谢产物的分离鉴定[J]. 昆虫学报, 2023, 66(10): 1282-1288.
	Yin CP, Bai XY, Abbas N, et al. Isolation and identification of actinomycete strain BYC-18 and its antimicrobial metabolites from the gut of Odontotermes formosanus(Isoptera: Termitidae)[J]. Acta Entomol Sin, 2023, 66(10): 1282-1288.
[16]	Wang WQ, Xiao GL, Du GZ, et al. Glutamicibacter halophytocola-mediated host fitness of potato tuber moth on Solanaceae crops[J]. Pest Manag Sci, 2022, 78(9): 3920-3930.
[17]	Cheng P, Xu K, Chen YC, et al. Cytotoxic aromatic polyketides from an insect derived Streptomyces sp. NA4286[J]. Tetrahedron Lett, 2019, 60(26): 1706-1709.
[18]	Kroiss J, Kaltenpoth M, Schneider B, et al. Symbiotic streptomycetes provide antibiotic combination prophylaxis for wasp offspring[J]. Nat Chem Biol, 2010, 6(4): 261-263.
[19]	Koehler S, Doubský J, Kaltenpoth M. Dynamics of symbiont-mediated antibiotic production reveal efficient long-term protection for beewolf offspring[J]. Front Zool, 2013, 10(1): 3.
[20]	Moore SJ, Lai HG, Chee SM, et al. A Streptomyces venezuelae cell-free toolkit for synthetic biology[J]. ACS Synth Biol, 2021, 10(2): 402-411.
[21]	Haeder S, Wirth R, Herz H, et al. Candicidin-producing Streptomyces support leaf-cutting ants to protect their fungus garden against the pathogenic fungus Escovopsis[J]. Proc Natl Acad Sci USA, 2009, 106(12): 4742-4746.
[22]	Dhodary B, Spiteller D. Ammonia production by Streptomyces symbionts of Acromyrmex leaf-cutting ants strongly inhibits the fungal pathogen Escovopsis[J]. Microorganisms, 2021, 9(8): 1622.
[23]	Gutierrez-Espinoza CA, León-Quispe J. Actinomyces with anti-candida activity isolated from leaf-cutting ants Atta cephalotes(Formicidae: Myrmicinae: Attini)[J]. Rev Peru Med Exp Salud Publica, 2018, 35(4): 590-598.
[24]	Chang PT, Rao K, Longo LO, et al. Thiopeptide defense by an ant's bacterial symbiont[J]. J Nat Prod, 2020, 83(3): 725-729.
[25]	Zucchi TD, Guidolin AS, Cônsoli FL. Isolation and characterization of Actinobacteria ectosymbionts from Acromyrmex subterraneus brunneus(Hymenoptera, Formicidae)[J]. Microbiol Res, 2011, 166(1): 68-76.
[26]	Scott JJ, Oh DC, Yuceer MC, et al. Bacterial protection of beetle-fungus mutualism[J]. Science, 2008, 322(5898): 63.
[27]	Blodgett JAV, Oh DC, Cao SG, et al. Common biosynthetic origins for polycyclic tetramate macrolactams from phylogenetically diverse bacteria[J]. Proc Natl Acad Sci USA, 2010, 107(26): 11692-11697.
[28]	Santamaría RI, Martínez-Carrasco A, Sánchez de la Nieta R, et al. Characterization of actinomycetes strains isolated from the intestinal tract and feces of the larvae of the longhorn beetle Cerambyx welensii[J]. Microorganisms, 2020, 8(12): 2013.
[29]	Bérdy J. Thoughts and facts about antibiotics: where we are now and where we are heading[J]. J Antibiot, 2012, 65(8): 385-395.
[30]	Bartlett JG, Gilbert DN, Spellberg B. Seven ways to preserve the miracle of antibiotics[J]. Clin Infect Dis, 2013, 56(10): 1445-1450.
[31]	Olano C, Méndez C, Salas JA. Antitumor compounds from actinomycetes: from gene clusters to new derivatives by combinatorial biosynthesis[J]. Nat Prod Rep, 2009, 26(5): 628-660.
[32]	Hopwood DA. Streptomyces in nature and medicine: the antibiotic makers[M]. Oxford: Oxford University Press, 2007
[33]	van der Heul HU, Bilyk BL, McDowall KJ, et al. Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era[J]. Nat Prod Rep, 2018, 35(6): 575-604.
[34]	Barka EA, Vatsa P, Sanchez L, et al. Taxonomy, physiology, and natural products of Actinobacteria[J]. Microbiol Mol Biol Rev, 2016, 80(1): 1-43.
[35]	Qin ZW, Munnoch JT, Devine R, et al. Formicamycins, antibacterial polyketides produced by Streptomyces formicae isolated from African Tetraponera plant-ants[J]. Chem Sci, 2017, 8(4): 3218-3227.
[36]	Ramachandran GN, Sasisekharan V. Conformation of polypeptides and proteins[J]. Adv Protein Chem, 1968, 23: 283-438.
[37]	Kricheldorf HR. Polypeptides and 100 years of chemistry of α-amino acid N-carboxyanhydrides[J]. Angew Chem Int Ed, 2006, 45(35): 5752-5784.
[38]	Chatterjee S, Roy RS, Balaram P. Expanding the polypeptide backbone: hydrogen-bonded conformations in hybrid polypeptides containing the higher homologues of alpha-amino acids[J]. J R Soc Interface, 2007, 4(15): 587-606.
[39]	Muttenthaler M, King GF, Adams DJ, et al. Trends in peptide drug discovery[J]. Nat Rev Drug Discov, 2021, 20(4): 309-325.
[40]	Lee SR, Lee D, Yu JS, et al. Natalenamides A-C, cyclic tripeptides from the termite-associated Actinomadura sp. RB99[J]. Molecules, 2018, 23(11): 3003.
[41]	Benndorf R, Guo HJ, Sommerwerk E, et al. Natural products from Actinobacteria associated with fungus-growing termites[J]. Antibiotics, 2018, 7(3): 83.
[42]	Hwang S, Le LTHL, Jo SI, et al. Pentaminomycins C-E: cyclic pentapeptides as autophagy inducers from a mealworm beetle gut bacterium[J]. Microorganisms, 2020, 8(9): 1390.
[43]	Jiang SW, Piao CY, Yu Y, et al. Streptomyces capitiformicae sp. nov., a novel actinomycete producing angucyclinone antibiotics isolated from the head of Camponotus japonicus Mayr[J]. Int J Syst Evol Microbiol, 2018, 68(1): 118-124.
[44]	Yin CP, Jin LP, Li S, et al. Diversity and antagonistic potential of Actinobacteria from the fungus-growing termite Odontotermes formosanus[J]. 3 Biotech, 2019, 9(2): 45.
[45]	Schoenian I, Spiteller M, Ghaste M, et al. Chemical basis of the synergism and antagonism in microbial communities in the nests of leaf-cutting ants[J]. Proc Natl Acad Sci USA, 2011, 108(5): 1955-1960.
[46]	Shin YH, Bae S, Sim J, et al. Nicrophorusamides A and B, antibacterial chlorinated cyclic peptides from a gut bacterium of the carrion beetle Nicrophorus concolor[J]. J Nat Prod, 2017, 80(11): 2962-2968.
[47]	Menegatti C, Lourenzon VB, Rodríguez-Hernández D, et al. Meliponamycins: antimicrobials from stingless bee-associated Streptomyces sp[J]. J Nat Prod, 2020, 83(3): 610-616.
[48]	Shin YH, Ban YH, Kim TH, et al. Structures and biosynthetic pathway of coprisamides C and D, 2-alkenylcinnamic acid-containing peptides from the gut bacterium of the carrion beetle Silpha perforata[J]. J Nat Prod, 2021, 84(2): 239-246.
[49]	Oh DC, Poulsen M, Currie CR, et al. Dentigerumycin: a bacterial mediator of an ant-fungus symbiosis[J]. Nat Chem Biol, 2009, 5(6): 391-393.
[50]	Sit CS, Ruzzini AC, Van Arnam EB, et al. Variable genetic architectures produce virtually identical molecules in bacterial symbionts of fungus-growing ants[J]. Proc Natl Acad Sci USA, 2015, 112(43): 13150-13154.
[51]	Wyche TP, Ruzzini AC, Beemelmanns C, et al. Linear peptides are the major products of a biosynthetic pathway that encodes for cyclic depsipeptides[J]. Org Lett, 2017, 19(7): 1772-1775.
[52]	Joo SH. Cyclic peptides as therapeutic agents and biochemical tools[J]. Biomol Ther, 2012, 20(1): 19-26.
[53]	Bitzer J, Streibel M, Langer HJ, et al. First Y-type actinomycins from Streptomyces with divergent structure-activity relationships for antibacterial and cytotoxic properties[J]. Org Biomol Chem, 2009, 7(3): 444-450.
[54]	Davis WR, Gabbara S, Hupe D, et al. Actinomycin D inhibition of DNA strand transfer reactions catalyzed by HIV-1 reverse transcriptase and nucleocapsid protein[J]. Biochemistry, 1998, 37(40): 14213-14221.
[55]	Lu DD, Ren JW, Du QQ, et al. p-Terphenyls and actinomycins from a Streptomyces sp. associated with the larva of mud dauber wasp[J]. Nat Prod Res, 2021, 35(11): 1869-1873.
[56]	Song YJ, Zheng HB, Peng AH, et al. Strepantibins A-C: hexokinase II inhibitors from a mud dauber wasp associated Streptomyces sp[J]. J Nat Prod, 2019, 82(5): 1114-1119.
[57]	Hill CR, Jamieson D, Thomas HD, et al. Characterisation of the roles of ABCB1, ABCC1, ABCC2 and ABCG2 in the transport and pharmacokinetics of actinomycin D in vitro and in vivo[J]. Biochem Pharmacol, 2013, 85(1): 29-37.
[58]	Shin YH, Ban YH, Shin J, et al. Azetidine-bearing non-ribosomal peptides, bonnevillamides D and E, isolated from a carrion beetle-associated actinomycete[J]. J Org Chem, 2021, 86(16): 11149-11159.
[59]	Fukuda TTH, Helfrich EJN, Mevers E, et al. Specialized metabolites reveal evolutionary history and geographic dispersion of a multilateral symbiosis[J]. ACS Cent Sci, 2021, 7(2): 292-299.
[60]	Carr G, Poulsen M, Klassen JL, et al. Microtermolides A and B from termite-associated Streptomyces sp. and structural revision of vinylamycin[J]. Org Lett, 2012, 14(11): 2822-2825.
[61]	Beemelmanns C, Ramadhar TR, Kim KH, et al. Macrotermycins A-D, glycosylated macrolactams from a termite-associated Amycolatopsis sp. M39[J]. Org Lett, 2017, 19(5): 1000-1003.
[62]	Xiao YS, Zhang B, Zhang M, et al. Rifamorpholines A-E, potential antibiotics from locust-associated Actinobacteria Amycolatopsis sp. Hca4[J]. Org Biomol Chem, 2017, 15(18): 3909-3916.
[63]	Oh DC, Poulsen M, Currie CR, et al. Sceliphrolactam, a polyene macrocyclic lactam from a wasp-associated Streptomyces sp[J]. Org Lett, 2011, 13(4): 752-755.
[64]	Malmierca MG, Pérez-Victoria I, Martín J, et al. Cooperative involvement of glycosyltransferases in the transfer of amino sugars during the biosynthesis of the macrolactam sipanmycin by Streptomyces sp. strain CS149[J]. Appl Environ Microbiol, 2018, 84(18): e01462-e01418.
[65]	Shin YH, Beom JY, Chung B, et al. Bombyxamycins A and B, cytotoxic macrocyclic lactams from an intestinal bacterium of the silkworm Bombyx mori[J]. Org Lett, 2019, 21(6): 1804-1808.
[66]	曹莹莹. 链霉菌CJ0806次级代谢产物及抗乳腺癌活性研究[D]. 济南: 山东大学, 2023.
	Cao YY. Study on the secondary metabolites of Streptomyces sp. CJ0806 and its anti-breast cancer activity[D]. Ji'nan: Shandong University, 2023.
[67]	Long YH, Zhang Y, Huang F, et al. Diversity and antimicrobial activities of culturable actinomycetes from Odontotermes formosanus(Blattaria: Termitidae)[J]. BMC Microbiol, 2022, 22(1): 80.
[68]	Rohr J, Thiericke R. Angucycline group antibiotics[J]. Nat Prod Rep, 1992, 9(2): 103-137.
[69]	Guo ZK, Wang T, Guo Y, et al. Cytotoxic angucyclines from Amycolatopsis sp. HCa1, a rare Actinobacteria derived from Oxya chinensis[J]. Planta Med, 2011, 77(18): 2057-2060.
[70]	Zhang YL, Li S, Jiang DH, et al. Antifungal activities of metabolites produced by a termite-associated Streptomyces canus BYB02[J]. J Agric Food Chem, 2013, 61(7): 1521-1524.
[71]	Seipke RF, Hutchings MI. The regulation and biosynthesis of antimycins[J]. Beilstein J Org Chem, 2013, 9: 2556-2563.
[72]	卢贻会, 李帅, 周端顼, 等. 白蚁巢拮抗放线菌BYC01代谢产物的分离和鉴定[J]. 微生物学报, 2014, 54(7): 754-759.
	Lu YH, Li S, Zhou DX, et al. Isolation and identification of termitarium antagonistic actinomycetes BYC 01 and its active metabolites[J]. Acta Microbiol Sin, 2014, 54(7): 754-759.
[73]	Zhang L, Song T, Wu J, et al. Antibacterial and cytotoxic metabolites of termite-associated Streptomyces sp. BYF63[J]. J Antibiot, 2020, 73(11): 766-771.
[74]	Rodríguez-Hernández D, Melo WGP, Menegatti C, et al. Actinobacteria associated with stingless bees biosynthesize bioactive polyketides against bacterial pathogens[J]. New J Chem, 2019, 43(25): 10109-10117.
[75]	Grubbs KJ, Surup F, Biedermann PHW, et al. Cycloheximide-producing Streptomyces associated with Xyleborinus saxesenii and Xyleborus affinis fungus-farming Ambrosia beetles[J]. Front Microbiol, 2020, 11: 562140.
[76]	Rak Lee S, Schalk F, Schwitalla JW, et al. Polyhalogenation of isoflavonoids by the termite-associated Actinomadura sp. RB99[J]. J Nat Prod, 2020, 83(10): 3102-3110.
[77]	Bi SF, Guo ZK, Jiang N, et al. New alkaloid from Streptomyces koyangensis residing in Odontotermes formosanus[J]. J Asian Nat Prod Res, 2013, 15(4): 422-425.
[78]	Bi SF, Li F, Song YC, et al. New acrylamide and oxazolidin derivatives from a termite-associated Streptomyces sp[J]. Nat Prod Commun, 2011, 6(3): 353-355.
[79]	DeWaal D, Nogueira V, Terry AR, et al. Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin[J]. Nat Commun, 2018, 9(1): 446.
[80]	Kim SH, Kwon SH, Park SH, et al. Tripartin, a histone demethylase inhibitor from a bacterium associated with a dung beetle larva[J]. Org Lett, 2013, 15(8): 1834-1837.
[81]	Kang HR, Lee D, Benndorf R, et al. Termisoflavones A-C, isoflavonoid glycosides from termite-associated Streptomyces sp. RB1[J]. J Nat Prod, 2016, 79(12): 3072-3078.
[82]	Currie CR, Mueller UG, Malloch D. The agricultural pathology of ant fungus gardens[J]. Proc Natl Acad Sci USA, 1999, 96(14): 7998-8002.
[83]	Liu ZY, Ishikawa K, Sanada E, et al. Identification of antimycin A as a c-Myc degradation accelerator via high-throughput screening[J]. J Biol Chem, 2023, 299(9): 105083.
[84]	Vanner SA, Li X, Zvanych R, et al. Chemical and biosynthetic evolution of the antimycin-type depsipeptides[J]. Mol Biosyst, 2013, 9(11): 2712-2719.
[85]	Jana S, Heaven MR, Dahiya N, et al. Antimicrobial 405 nm violet-blue light treatment of ex vivo human platelets leads to mitochondrial metabolic reprogramming and potential alteration of Phospho-proteome[J]. J Photochem Photobiol B, 2023, 241: 112672.
[86]	Han YH, Kim SH, Kim SZ, et al. Antimycin A as a mitochondria damage agent induces an S phase arrest of the cell cycle in HeLa cells[J]. Life Sci, 2008, 83(9/10): 346-355.
[87]	Mendes TD, Borges WS, Rodrigues A, et al. Anti-Candida properties of urauchimycins from Actinobacteria associated with trachymyrmex ants[J]. Biomed Res Int, 2013, 2013: 835081.
[88]	Ortega HE, Ferreira LLG, Melo WGP, et al. Antifungal compounds from Streptomyces associated with attine ants also inhibit Leishmania donovani[J]. PLoS Negl Trop Dis, 2019, 13(8): e0007643.
[89]	Ortega HE, Lourenzon VB, Chevrette MG, et al. Antileishmanial macrolides from ant-associated Streptomyces sp. ISID311[J]. Bioorg Med Chem, 2021, 32: 116016.
[90]	Barke J, Seipke RF, Grüschow S, et al. A mixed community of actinomycetes produce multiple antibiotics for the fungus farming ant Acromyrmex octospinosus[J]. BMC Biol, 2010, 8: 109.
[91]	Van Arnam EB, Ruzzini AC, Sit CS, et al. Selvamicin, an atypical antifungal polyene from two alternative genomic contexts[J]. Proc Natl Acad Sci USA, 2016, 113(46): 12940-12945.
[92]	Pandey RC, Narasimhachari N, Rinehart KL Jr, et al. Polyene antibiotics. IV. structure of Chainin[J]. J Am Chem Soc, 1972, 94(12): 4306-4310.
[93]	Gao H, Grüschow S, Barke J, et al. Filipins: the first antifungal “weed killers” identified from bacteria isolated from the trap-ant[J]. RSC Adv, 2014, 4(100): 57267-57270.
[94]	Li JJ, Sang ML, Jiang YT, et al. Polyene-producing Streptomyces spp. from the fungus-growing termite Macrotermes barneyi exhibit high inhibitory activity against the antagonistic fungus Xylaria[J]. Front Microbiol, 2021, 12: 649962.
[95]	Cao TT, Mu S, Lu C, et al. Streptomyces amphotericinicus sp. nov., an amphotericin-producing actinomycete isolated from the head of an ant(Camponotus japonicus Mayr)[J]. Int J Syst Evol Microbiol, 2017, 67(12): 4967-4973.
[96]	Qiao LQ, Dong Y, Zhou HL, et al. Effect of post-polyketide synthase modification groups on property and activity of polyene macrolides[J]. Antibiotics, 2023, 12(1): 119.
[97]	Kim KH, Ramadhar TR, Beemelmanns C, et al. Natalamycin A, an ansamycin from a termite-associated Streptomyces sp[J]. Chem Sci, 2014, 5(11): 4333-4338.
[98]	Gui M, Zhang MX, Wu WH, et al. Natural occurrence, bioactivity and biosynthesis of elaiophylin analogues[J]. Molecules, 2019, 24(21): 3840.
[99]	Klassen JL, Lee SR, Poulsen M, et al. Efomycins K and L from a termite-associated Streptomyces sp. M56 and their putative biosynthetic origin[J]. Front Microbiol, 2019, 10: 1739.
[100]	An JS, Lee JY, Kim E, et al. Formicolides A and B, antioxidative and antiangiogenic 20-membered macrolides from a wood ant gut bacterium[J]. J Nat Prod, 2020, 83(9): 2776-2784.
[101]	An JS, Lim HJ, Lee JY, et al. Hamuramicin C, a cytotoxic bicyclic macrolide isolated from a wasp gut bacterium[J]. J Nat Prod, 2022, 85(4): 936-942.
[102]	Yan YM, Li X, Zhang CH, et al. Research progress on antibacterial activities and mechanisms of natural alkaloids: a review[J]. Antibiotics, 2021, 10(3): 318.
[103]	Schäfer H, Wink M. Medicinally important secondary metabolites in recombinant microorganisms or plants: progress in alkaloid biosynthesis[J]. Biotechnol J, 2009, 4(12): 1684-1703.
[104]	Um S, Bach DH, Shin B, et al. Naphthoquinone-oxindole alkaloids, coprisidins A and B, from a gut-associated bacterium in the dung beetle, Copris tripartitus[J]. Org Lett, 2016, 18(22): 5792-5795.
[105]	曾还雄. 两株蜚蠊肠道内生放线菌次级代谢产物的初步研究[D]. 广州: 广东药科大学, 2019.
	Zeng HX. Preliminary study on secondary metabolites of two cockroach gut endophytic actinomycetes[D]. Guangzhou: Guangdong Pharmaceutical University, 2019.
[106]	Hong SH, Ban YH, Byun WS, et al. Camporidines A and B: antimetastatic and anti-inflammatory polyketide alkaloids from a gut bacterium of Camponotus kiusiuensis[J]. J Nat Prod, 2019, 82(4): 903-910.
[107]	Guo HJ, Benndorf R, Leichnitz D, et al. Isolation, biosynthesis and chemical modifications of rubterolones A-F: rare tropolone alkaloids from Actinomadura sp. 5-2[J]. Chemistry, 2017, 23(39): 9338-9345.
[108]	Guo HJ, Benndorf R, König S, et al. Expanding the rubterolone family: intrinsic reactivity and directed diversification of PKS-derived pyrans[J]. Chemistry, 2018, 24(44): 11319-11324.
[109]	Zakalyukina YV, Birykov MV, Lukianov DA, et al. Nybomycin-producing Streptomyces isolated from carpenter ant Camponotus vagus[J]. Biochimie, 2019, 160: 93-99.
[110]	Lin ZH, Xu XB, Zhao S, et al. Total synthesis and antimicrobial evaluation of natural albomycins against clinical pathogens[J]. Nat Commun, 2018, 9(1): 3445.
[111]	Zakalyukina YV, Pavlov NA, Lukianov DA, et al. A new albomycin-producing strain of Streptomyces globisporus subsp. globisporus may provide protection for ants Messor structor[J]. Insects, 2022, 13(11): 1042.
[112]	Kim SH, Ko H, Bang HS, et al. Coprismycins A and B, neuroprotective phenylpyridines from the dung beetle-associated bacterium, Streptomyces sp[J]. Bioorg Med Chem Lett, 2011, 21(19): 5715-5718.
[113]	Zhou LF, Wu J, Li S, et al. Antibacterial potential of termite-associated Streptomyces spp[J]. ACS Omega, 2021, 6(6): 4329-4334.
[114]	Prado-Alonso L, Pérez-Victoria I, Malmierca MG, et al. Colibrimycins, novel halogenated hybrid polyketide synthase-nonribosomal peptide synthetase(PKS-NRPS)compounds produced by Streptomyces sp. strain CS147[J]. Appl Environ Microbiol, 2022, 88(1): e0183921.
[115]	Van Arnam EB, Ruzzini AC, Sit CS, et al. A rebeccamycin analog provides plasmid-encoded niche defense[J]. J Am Chem Soc, 2015, 137(45): 14272-14274.
[116]	van der Meij A, Worsley SF, Hutchings MI, et al. Chemical ecology of antibiotic production by actinomycetes[J]. FEMS Microbiol Rev, 2017, 41(3): 392-416.
[117]	Diarra U, Osborne-Naikatini T, Subramani R. Actinomycetes associated with hymenopteran insects: a promising source of bioactive natural products[J]. Front Microbiol, 2024, 15: 1303010.
[118]	Kaltenpoth M, Schmitt T, Polidori C, et al. Symbiotic streptomycetes in antennal glands of the South American digger wasp genus Trachypus(Hymenoptera, Crabronidae)[J]. Physiol Entomol, 2010, 35(2): 196-200.
[119]	Kaltenpoth M, Göttler W, Herzner G, et al. Symbiotic bacteria protect wasp larvae from fungal infestation[J]. Curr Biol, 2005, 15(5): 475-479.
[120]	Seipke RF, Barke J, Brearley C, et al. A single Streptomyces symbiont makes multiple antifungals to support the fungus farming ant Acromyrmex octospinosus[J]. PLoS One, 2011, 6(8): e22028.
[121]	Baranova AA, Zakalyukina YV, Ovcharenko AA, et al. Antibiotics from insect-associated Actinobacteria[J]. Biology, 2022, 11(11): 1676.
[122]	Kaltenpoth M, Engl T. Defensive microbial symbionts in Hymenoptera[J]. Funct Ecol, 2014, 28(2): 315-327.
[123]	Yarzábal LA, Salazar LMB, Batista-García RA. Climate change, melting cryosphere and frozen pathogens: should we worry…?[J]. Environ Sustain(Singap), 2021, 4(3): 489-501.
[124]	Ma CC, Wang ZL, Xu T, et al. The approved gene therapy drugs worldwide: from 1998 to 2019[J]. Biotechnol Adv, 2020, 40: 107502.
[125]	Berdy B, Spoering AL, Ling LL, et al. In situ cultivation of previously uncultivable microorganisms using the ichip[J]. Nat Protoc, 2017, 12(10): 2232-2242.
[126]	Sudakaran S, Salem H, Kost C, et al. Geographical and ecological stability of the symbiotic mid-gut microbiota in European firebugs, Pyrrhocoris apterus(Hemiptera, Pyrrhocoridae)[J]. Mol Ecol, 2012, 21(24): 6134-6151.