AccScience Publishing / CP / Volume 5 / Issue 2 /
Submit to CP
Cite this article
65
Download
1035
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
REVIEW

Non-ribosomally synthesized lipopeptides: Promising novel therapeutics for cancer treatment

Md. Asaduzzaman Shishir1,2* ,  Sanjida Sultana2 ,  Jabin Taj Turna2 ,  Tanjina Akter2 ,  Sayma Jahan Mim2 ,  Rashedul Islam2 ,  Md. Tanvir2 ,  Yeasmin Akther2 ,  Israt Jahan2 ,  Umme Tamanna Ferdous3 ,  Musharrat Jahan Prima4 ,  Md. Fakruddin5
Show Less
1 Department of Microbiology, Dhaka International University, Dhaka-1212, Bangladesh
2 Department of Microbiology, Primeasia University, Dhaka-1213, Bangladesh
3 Aquatic Animal Health and Therapeutics Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
4 Department of Physiology, Asan-Minnesota Institute for Innovating Transplantation, Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Korea
5 Department of Biochemistry and Microbiology, North South University, Dhaka-1229, Bangladesh
CP 2023, 5(2), 2569
Submitted: 12 April 2023 | Accepted: 15 June 2023 | Published: 29 June 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Bacteria-derived non-ribosomally synthesized lipopeptides (NRLPs) present promising potential for cancer treatment, alongside their known antimicrobial, anti-inflammatory, and other pharmacological effects, due to their unique properties and modular assembly. However, addressing challenges such as toxicity, pharmacokinetics, and regulatory considerations necessitates an in-depth understanding of lipopeptides. This review provides extensive insights into the modular synthesis pathways, molecular mechanisms, structural diversity, and bioactivities of NRLPs. It highlights the remarkable potential of these lipopeptides as innovative therapeutic agents for cancer treatment. A significant portion of the review is dedicated to unraveling the sources, types, and bioactivities of NRLPs, with particular emphasis on their anti-cancer properties. The mechanisms underlying their efficacy against cancer cells, including apoptosis induction, cell cycle modulation, and interference with signaling pathways, are discussed. Envisioning the future of cancer therapeutics, the review concludes by outlining strategies for improved peptide design, integration with existing therapies, innovative and targeted cancer treatments, and the incorporation of emerging technologies. This comprehensive overview underscores the transformative potential of NRLPs in reshaping the landscape of cancer treatment.

Keywords
Non-ribosomally synthesized lipopeptides
Non-ribosomally synthesized lipopeptide
Synthesis
Cytotoxicity
Anticancer drugs
Funding
None.
References
  1. Liu X, Tao X, Zou A, Yang S, Zhang L, Mu B. Effect of the microbial lipopeptide on tumor cell lines: Apoptosis induced by disturbing the fatty acid composition of cell membrane. Protein Cell. 2010;1(6):584-594. doi: 10.1007/s13238-010-0072-4

 

  1. Tank JG, Pandya RV. Anti-proliferative activity of surfactins on human cancer cells and their potential use in therapeutics. Peptides. 2022;155:170836. doi: 10.1016/j.peptides.2022.170836

 

  1. Yin H, Guo C, Wang Y, et al. Fengycin inhibits the growth of the human lung cancer cell line 95D through reactive oxygen species production and mitochondria-dependent apoptosis. Anticancer Drugs. 2013;24(6):587-598. doi: 10.1097/CAD.0b013e3283611395

 

  1. Akhi MA, Ferdous UT, Fakruddin M, Datta S, Shishir MA. In silico evaluation of potential ligands of cancer cells for surfactin from Bacillus spp. Proc Anticancer Res. 2023;7(3):18-28.

 

  1. Cummings MJ. Harnessing Synthetic Biology for the Bioprospecting and Engineering of Aromatic Polyketide Synthases. United Kingdom: The University of Manchester; 2018.

 

  1. Dimise EJ. The Discovery, Isolation, Structure Elucidation and Total Synthesis of the Fuscachelins, Nonribosomal Peptide Siderophores form the Thermophilic Actinomycete Thermobifida fusca. United States: Boston College; 2010.

 

  1. Roongsawang N, Washio K, Morikawa M. Diversity of nonribosomal peptide synthetases involved in the biosynthesis of lipopeptide biosurfactants. Int J Mol Sci. 2010;12(1):141-172. doi: 10.3390/ijms12010141

 

  1. Li Z, de Vries RH, Chakraborty P, et al. Novel modifications of nonribosomal peptides from Brevibacillus laterosporus MG64 and investigation of their mode of action. Appl Environ Microbiol. 2020;86(24):e01981-20. doi: 10.1128/AEM.01981-20

 

  1. Kleijn LHJ, Martin NI. The cyclic lipopeptide antibiotics. Antibacterials. 2018;2:27-53.

 

  1. Meena KR, Sharma A, Kanwar SS. Microbial lipopeptides and their medical applications. Ann Pharmacol Pharm. 2017;2(11):1111.

 

  1. Zhao H, Shao D, Jiang C, et al. Biological activity of lipopeptides from Bacillus. Appl Microbiol Biotechnol. 2017;101:5951-5960. doi: 10.1007/s00253-017-8396-0

 

  1. Choi SYC, Lin D, Gout PW, Collins CC, Xu Y, Wang Y. Lessons from patient-derived xenografts for better in vitro modeling of human cancer. Adv Drug Deliv Rev. 2014;79:222-237. doi: 10.1016/j.addr.2014.09.009

 

  1. Wen H, Jung H, Li X. Drug delivery approaches in addressing clinical pharmacology-related issues: Opportunities and challenges. AAPS J. 2015;17:1327-1340. doi: 10.1208/s12248-015-9814-9

 

  1. Czechowicz P, Nowicka J. Antimicrobial activity of lipopeptides. Postępy Mikrobiol Microbiol. 2018;57(3):213-227.

 

  1. Mnif I, Ghribi D. Review lipopeptides biosurfactants: Mean classes and new insights for industrial, biomedical, and environmental applications. Pept Sci. 2015;104(3):129-147. doi: 10.1002/bip.22630

 

  1. Patel S, Ahmed S, Eswari JS. Therapeutic cyclic lipopeptides mining from microbes: Latest strides and hurdles. World J Microbiol Biotechnol. 2015;31(8):1177-1193. doi: 10.1007/s11274-015-1880-8

 

  1. Steenbergen JN, Alder J, Thorne GM, Tally FP. Daptomycin: A lipopeptide antibiotic for the treatment of serious Gram-positive infections. J Antimicrob Chemother. 2005;55(3):283-288. doi: 10.1093/jac/dkh546

 

  1. Robbel L, Marahiel MA. Daptomycin, a bacterial lipopeptide synthesized by a nonribosomal machinery. J Biol Chem. 2010;285(36):27501-27508. doi: 10.1074/jbc.R110.128181

 

  1. Gross H, Loper JE. Genomics of secondary metabolite production by Pseudomonas spp. Nat Prod Rep. 2009;26(11):1408-1446. doi: 10.1039/b817075b

 

  1. Meena KR, Kanwar SS. Lipopeptides as the antifungal and antibacterial agents: Applications in food safety and therapeutics. Biomed Res Int. 2015;2015:473050. doi: 10.1155/2015/473050

 

  1. Shah RD, Wunderink RG. Viral pneumonia and acute respiratory distress syndrome. Clin Chest Med. 2017;38(1):113-125. doi: 10.1016/j.ccm.2016.11.013

 

  1. Demay J, Bernard C, Reinhardt A, Marie B. Natural products from cyanobacteria: Focus on beneficial activities. Mar Drugs. 2019;17(6):320. doi: 10.3390/md17060320

 

  1. Jakubczyk D, Dussart F. Selected fungal natural products with antimicrobial properties. Molecules. 2020;25(4):911. doi: 10.3390/molecules25040911

 

  1. Wang Z, Liu C, Shi Y, et al. Classification, application, multifarious activities and production improvement of lipopeptides produced by Bacillus. Crit Rev Food Sci Nutr. 2023:1-14.

 

  1. Yaraguppi DA, Bagewadi ZK, Mahanta N, et al. gene expression and characterization of iturin a lipopeptide biosurfactant from Bacillus aryabhattai for enhanced oil recovery. Gels. 2022;8(7):403. doi: 10.3390/gels8070403

 

  1. Hahn M, Stachelhaus T. Selective interaction between nonribosomal peptide synthetases is facilitated by short communication-mediating domains. Proc Natl Acad Sci U S A. 2004;101(44):15585-15590. doi: 10.1073/pnas.0404932101

 

  1. Fischbach MA, Walsh CT. Assembly-line enzymology for polyketide and nonribosomal peptide antibiotics: Logic, machinery, and mechanisms. Chem Rev. 2006;106(8):3468-3496. doi: 10.1021/cr0503097

 

  1. Bergendahl V, Linne U, Marahiel MA. Mutational analysis of the C‐domain in nonribosomal peptide synthesis. Eur J Biochem. 2002;269(2):620-629. doi: 10.1046/j.0014-2956.2001.02691.x

 

  1. Mootz HD, Marahiel MA. The tyrocidine biosynthesis operon of Bacillus brevis: Complete nucleotide sequence and biochemical characterization of functional internal adenylation domains. J Bacteriol. 1997;179(21):6843-6850. doi: 10.1128/jb.179.21.6843-6850.1997

 

  1. Lambalot RH, Gehring AM, Flugel RS, et al. A new enzyme superfamily-the phosphopantetheinyl transferases. Chem Biol. 1996;3(11):923-936. doi: 10.1016/s1074-5521(96)90181-7

 

  1. Rausch C, Hoof I, Weber T, Wohlleben W, Huson DH. Phylogenetic analysis of condensation domains in NRPS sheds light on their functional evolution. BMC Evol Biol. 2007;7:78. doi: 10.1186/1471-2148-7-78

 

  1. Ali N, Pang Z, Wang F, Xu B, El-Seedi HR. Lipopeptide biosurfactants from Bacillus Spp.: Types, production, biological activities, and applications in food. J Food Qual. 2022;2022:3930112.

 

  1. Finking R, Marahiel MA. Biosynthesis of nonribosomal peptides. Annu Rev Microbiol. 2004;58:453-488. doi: 10.1146/annurev.micro.58.030603.123615

 

  1. Miller DA, Luo L, Hillson N, Keating TA, Walsh CT. Yersiniabactin synthetase: A four-protein assembly line producing the nonribosomal peptide/polyketide hybrid siderophore of Yersinia pestis. Chem Biol. 2002;9(3):333-344. doi: 10.1016/s1074-5521(02)00115-1

 

  1. Trauger JW, Kohli RM, Mootz HD, Marahiel MA, Walsh CT. Peptide cyclization catalysed by the thioesterase domain of tyrocidine synthetase. Nature. 2000;407(6801):215-218. doi: 10.1038/35025116

 

  1. Konz D, Klens A, Schörgendorfer K, Marahiel MA. The bacitracin biosynthesis operon of Bacillus licheniformis ATCC 10716: Molecular characterization of three multi-modular peptide synthetases. Chem Biol. 1997;4(12):927-937. doi: 10.1016/s1074-5521(97)90301-x

 

  1. Hamley IW, Dehsorkhi A, Jauregi P, et al. Self-assembly of three bacterially-derived bioactive lipopeptides. Soft Matter. 2013;9(40):9572-9578.

 

  1. Hsieh FC, Li MC, Lin TC, Kao SS. Rapid detection and characterization of surfactin-producing Bacillus subtilis and closely related species based on PCR. Curr Microbiol. 2004;49:186-191.

 

  1. Wu X, Wu X, Sun Q, et al. Progress of small molecular inhibitors in the development of anti-influenza virus agents. Theranostics. 2017;7(4):826-845. doi: 10.7150/thno.17071

 

  1. Eyéghé-Bickong HA. Role of Surfactin from Bacillus subtilis in Protection Against Antimicrobial Peptides Produced by Bacillus Species. Stellenbosch: University of Stellenbosch; 2011.

 

  1. Horak I, Engelbrecht G, van Rensburg PJJ, Claassens S. Microbial metabolomics: Essential definitions and the importance of cultivation conditions for utilizing Bacillus species as bionematicides. J Appl Microbiol. 2019;127(2):326-343. doi: 10.1111/jam.14218

 

  1. Grangemard I, Wallach J, Maget-Dana R, Peypoux F. Lichenysin: A more efficient cation chelator than surfactin. Appl Biochem Biotechnol. 2001;90:199-210. doi: 10.1385/abab:90:3:199

 

  1. Qiu Y, Xiao F, Wei X, Wen Z, Chen S. Improvement of lichenysin production in Bacillus licheniformis by replacement of native promoter of lichenysin biosynthesis operon and medium optimization. Appl Microbiol Biotechnol. 2014;98:8895-8903. doi: 10.1007/s00253-014-5978-y

 

  1. Madslien EH, Rønning HT, Lindbäck T, Hassel B, Andersson MA, Granum PE. Lichenysin is produced by most Bacillus licheniformis strains. J Appl Microbiol. 2013;115(4):1068-1080. doi: 10.1111/jam.12299

 

  1. Hathout Y, Ho YP, Ryzhov V, Demirev P, Fenselau C. Kurstakins: A new class of Lipopeptides isolated from Bacillus thuringiensis. J Nat Prod. 2000;63(11):1492-1496. doi: 10.1021/np000169q

 

  1. Maget-Dana R, Peypoux F. Iturins, a special class of pore-forming lipopeptides: Biological and physicochemical properties. Toxicology. 1994;87(1-3):151-174. doi: 10.1016/0300-483x(94)90159-7

 

  1. Pons IM. Antimicrobial Activity in Bacillus spp. from Plant Environments against Plant Pathogens. Relationship with Cyclic Lipopeptide Genes and Products. Universitat de Girona, Doctoral Dissertation, 2013.

 

  1. Cozzolino ME, Distel JS, García PA, et al. Control of postharvest fungal pathogens in pome fruits by lipopeptides from a Bacillus sp. isolate SL-6. Sci Hortic (Amsterdam). 2020;261:108957.

 

  1. Cochrane SA, Vederas JC. Lipopeptides from Bacillus and Paenibacillus spp.: A gold mine of antibiotic candidates. Med Res Rev. 2016;36(1):4-31. doi: 10.1002/med.21321

 

  1. Hanif A, Zhang F, Li P, et al. Fengycin produced by Bacillus amyloliquefaciens FZB42 inhibits Fusarium graminearum growth and mycotoxins biosynthesis. Toxins (Basel). 2019;11(5):295. doi: 10.3390/toxins11050295

 

  1. Pathak K V, Keharia H, Gupta K, Thakur SS, Balaram P. Lipopeptides from the banyan endophyte, Bacillus subtilis K1: Mass spectrometric characterization of a library of fengycins. J Am Soc Mass Spectrom. 2012;23(10):1716-1728. doi: 10.1007/s13361-012-0437-4

 

  1. Hussein W. Fengycin or plipastatin? A confusing question in Bacilli. Biotechnol J Biotechnol Comput Biol Bionanotechnol. 2019;100(1):47-55.

 

  1. Balleza D, Alessandrini A, Beltrán García MJ. Role of lipid composition, physicochemical interactions, and membrane mechanics in the molecular actions of microbial cyclic lipopeptides. J Membr Biol. 2019;252(2-3):131-157. doi: 10.1007/s00232-019-00067-4

 

  1. Patel A, Bah MA, Weiner DB. In vivo delivery of nucleic acid-encoded monoclonal antibodies. BioDrugs. 2020;34(3):273-293. doi: 10.1007/s40259-020-00412-3

 

  1. Raucher D, Moktan S, Massodi I, Bidwell GL 3rd. Therapeutic peptides for cancer therapy. Part II-cell cycle inhibitory peptides and apoptosis-inducing peptides. Expert Opin Drug Deliv. 2009;6(10):1049-1064. doi: 10.1517/17425240903158909

 

  1. Zhao H, Yan L, Xu X, et al. Potential of Bacillus subtilis lipopeptides in anti-cancer I: induction of apoptosis and paraptosis and inhibition of autophagy in K562 cells. AMB Express. 2018;8(1):78. doi: 10.1186/s13568-018-0606-3

 

  1. Jacques P. Surfactin and other Lipopeptides from Bacillus Spp. Biosurfactants from Genes to Application. Berlin: Springer; 2011. p. 57-91.

 

  1. Dey G, Bharti R, Dhanarajan G, et al. Marine lipopeptide Iturin A inhibits Akt mediated GSK3β and FoxO3a signaling and triggers apoptosis in breast cancer. Sci Rep. 2015;5(1):10316. doi: 10.1038/srep10316

 

  1. Inès M, Dhouha G. Lipopeptide surfactants: Production, recovery and pore forming capacity. Peptides. 2015;71:100-112. doi: 10.1016/j.peptides.2015.07.006

 

  1. Park SY, Kim JH, Lee YJ, Lee SJ, Kim Y. Surfactin suppresses TPA-induced breast cancer cell invasion through the inhibition of MMP-9 expression. Int J Oncol. 2013;42(1):287-296. doi: 10.3892/ijo.2012.1695

 

  1. Seydlová G, Svobodová J. Review of surfactin chemical properties and the potential biomedical applications. Cent Eur J Med. 2008;3:123-133.

 

  1. Wang SQ, Du QS, Zhao K, Li AX, Wei DQ, Chou KC. Virtual screening for finding natural inhibitor against cathepsin-L for SARS therapy. Amino Acids. 2007;33(1):129-135. doi: 10.1007/s00726-006-0403-1

 

  1. Ferdous UT, Shishir MA, Khan SN, Hoq MM. Bacillus spp.: Attractive sources of anti-cancer and anti-proliferative biomolecules. Microb Bioact. 2018;1(1):E033-E045. doi: 10.25163/microbbioacts.11005B0408130818

 

  1. Dan AK, Manna A, Ghosh S, et al. Molecular mechanisms of the lipopeptides from Bacillus subtilis in the apoptosis of cancer cells - A review on its current status in different cancer cell lines. Adv Cancer Biol Metastasis. 2021;3:100019.

 

  1. Routhu SR, Nagarjuna Chary R, Shaik AB, Prabhakar S, Ganesh Kumar C, Kamal A. Induction of apoptosis in lung carcinoma cells by antiproliferative cyclic lipopeptides from marine algicolous isolate Bacillus atrophaeus strain AKLSR1. Process Biochem. 2019;79:142-154.

 

  1. Dey G, Bharti R, Sen R, Mandal M. Microbial amphiphiles: A class of promising new-generation anticancer agents. Drug Discov Today. 2015;20(1):136-146. doi: 10.1016/j.drudis.2014.09.006

 

  1. Hajare SN, Subramanian M, Gautam S, Sharma A. Induction of apoptosis in human cancer cells by a Bacillus lipopeptide bacillomycin D. Biochimie. 2013;95(9):1722-1731. doi: 10.1016/j.biochi.2013.05.015

 

  1. Ledger EVK, Sabnis A, Edwards AM. Polymyxin and lipopeptide antibiotics: Membrane-targeting drugs of last resort. Microbiology (Reading). 2022;168(2):001136. doi: 10.1099/mic.0.001136

 

  1. Fierer DS, Dieterich DT, Mullen MP, et al. Telaprevir in the treatment of acute hepatitis C virus infection in HIV-infected men. Clin Infect Dis. 2014;58(6):873-879. doi: 10.1093/cid/cit799

 

  1. Qu J, Qi TT, Qu Q, et al. Polymyxin B-based regimens for patients infected with carbapenem-resistant gram-negative bacteria: Clinical and microbiological efficacy, mortality, and safety. Infect Drug Resist. 2022;15:1205-1218. doi: 10.2147/IDR.S357746

 

  1. Liu J, Li W, Zhu X, et al. Surfactin effectively inhibits Staphylococcus aureus adhesion and biofilm formation on surfaces. Appl Microbiol Biotechnol. 2019;103(11):4565-4574. doi: 10.1007/s00253-019-09808-w

 

  1. Xie L, Zhang W, Liu Z, Cai Y, Li Y, Fang X. Open acces characterization of a new highly toxic isolate of Bacillus thuringiensis from the diapausing larvae of silkworm and identification of cry1A 22 gene. Bt Res. 2010;1(1):1-9.

 

  1. Moretta A, Scieuzo C, Petrone AM, et al. Antimicrobial peptides: A new hope in biomedical and pharmaceutical fields. Front Cell Infect Microbiol. 2021;11:668632. doi: 10.3389/fcimb.2021.668632

 

  1. Atangcho L, Navaratna T, Thurber GM. Hitting undruggable targets: Viewing stabilized peptide development through the lens of quantitative systems pharmacology. Trends Biochem Sci. 2019;44(3):241-257. doi: 10.1016/j.tibs.2018.11.008

 

  1. Ciulla MG, Civera M, Sattin S, Kumar K. Nature-inspired and medicinally relevant short peptides. Explor Drug Sci. 2023;1:140-171.

 

  1. Jafari SM, McClements DJ. In: Toldrá FB, editor. Nanotechnology Approaches for Increasing Nutrient Bioavailability. Ch. 1. Academic Press; 2017. p. 1-30. Available from: https://www.sciencedirect.com/science/ article/pii/S1043452616300766 [Last accessed 2013 Apr 03].

 

  1. Bruno BJ, Miller GD, Lim CS. Basics and recent advances in peptide and protein drug delivery. Ther Deliv. 2013;4(11):1443-1467. doi: 10.4155/tde.13.104

 

  1. Vergote V, Burvenich C, Van de Wiele C, De Spiegeleer B. Quality specifications for peptide drugs: A regulatory‐pharmaceutical approach. J Pept Sci. 2009;15(11):697-710. doi: 10.1002/psc.1167

 

  1. Bozhüyük KAJ, Linck A, Tietze A, et al. Modification and de novo design of non-ribosomal peptide synthetases using specific assembly points within condensation domains. Nat Chem. 2019;11(7):653-661. doi: 10.1038/s41557-019-0276-z

 

  1. Johnston CW, Badran AH. Natural and engineered precision antibiotics in the context of resistance. Curr Opin Chem Biol. 2022;69:102160. doi: 10.1016/j.cbpa.2022.102160

 

  1. Ongey EL, Neubauer P. Lanthipeptides: Chemical synthesis versus in vivo biosynthesis as tools for pharmaceutical production. Microb Cell Fact. 2016;15(1):97. doi: 10.1186/s12934-016-0502-y

 

  1. Zhang Y, Fang Z, Li R, Huang X, Liu Q. Design of outer membrane vesicles as cancer vaccines: A new toolkit for cancer therapy. Cancers (Basel). 2019;11(9):1314. doi: 10.3390/cancers11091314

 

  1. Medema MH, de Rond T, Moore BS. Mining genomes to illuminate the specialized chemistry of life. Nat Rev Genet. 2021;22(9):553-571. doi: 10.1038/s41576-021-00363-7

 

  1. Yadav M, Eswari JS. Opportunistic challenges of computer-aided drug discovery of lipopeptides: New insights for large molecule therapeutics. Avicenna J Med Biotechnol. 2023;15(1):3-13. doi: 10.18502/ajmb.v15i1.11419

 

  1. Lath A, Santal AR, Kaur N, Kumari P, Singh NP. Anti-cancer peptides: Their current trends in the development of peptide-based therapy and anti-tumor drugs. Biotechnol Genet Eng Rev. 2023;39(1):45-84. doi: 10.1080/02648725.2022.2082157
Conflict of interest
The authors declare they have no competing interests.
Share
Back to top
Cancer Plus, Electronic ISSN: 2661-3840 Print ISSN: 2661-3832, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept