Biological activity of lipopeptides from Bacillus


The lipopeptides of Bacillus are small metabolites that contain a cyclic structure formed by 7–10 amino acids (including 2–4 d-amino acids) and a beta-hydroxy fatty acid with 13–19 C atoms. These lipopeptides exhibit a variety of biological activities, including interactions with biofilms, and anti-fungal, anti-inflammatory, anti-tumor, anti-virus, and anti-platelet properties. The multiple activities of lipopeptides have stimulated significant interest in the exploitation of these lipopeptides for use as antibiotics, feed additives, anti-tumor agents, urgent thrombolytic therapeutic agents, and drug delivery systems. Understanding the natural function of these structurally diverse lipopeptides in Bacillus provides insight into microbial regulatory programs and is required for efficient development of more effective products. Currently, there is still insufficient knowledge of the direct target of these lipopeptides, and continued efforts are needed to enhance their biosynthesis efficiency for industrial applications.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 199

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5


  1. Ajesh K, Sudarslal S, Arunan C, Sreejith K (2013) Kannurin, a novel lipopeptide from Bacillus cereus strain AK1: isolation, structural evaluation and antifungal activities. J Appl Microbiol 115(6):1287–1296. doi:10.1111/jam.12324

  2. Aranda FJ, Teruel JA, Ortiz A (2005) Further aspects on the hemolytic activity of the antibiotic lipopeptide iturin A. BBA-Biomembranes 1713(1):51–56. doi:10.1016/j.bbamem.2005.05.003

  3. Arima K, Kakinuma A, Tamura G (1968) Surfactin, a crystalline peptide lipid surfactant produced by Bacillus subtilis: isolation, characterization and its inhibition of fibrin clot formation. Biochem Biophys Res Commun 31(3):488–494. doi:10.1016/0006-291X(68)90503-2

  4. Banat IM, De Rienzo MA, Quinn GA (2014) Microbial biofilms: biosurfactants as antibiofilm agents. Appl Microbiol Biotechnol 98(24):9915–9929. doi:10.1007/s00253-014-6169-6

  5. Besson F, Michel G (1987) Isolation and characterization of new iturins: iturin D and iturin E. J Antibiot 40(4):437–442. doi:10.7164/antibiotics.40.437

  6. Byeon SE, Lee YG, Kim BH, Shen T, Lee SY, Park HJ, Park SC, Rhee MH, Cho JY (2008) Surfactin blocks NO production in lipopolysaccharide-activated macrophages by inhibiting NF-kappaB activation. J Microbiol Biotechnol 18(12):1984–1989

  7. Cao XH, Wang AH, Wang CL, Mao DZ, Lu MF, Cui YQ, Jiao RZ (2010) Surfactin induces apoptosis in human breast cancer MCF-7 cells through a ROS/JNK-mediated mitochondrial/caspase pathway. Chem Biol Interact 183(3):357–362. doi:10.1016/j.cbi.2009.11.027

  8. Chen Y, Yan F, Chai Y, Liu H, Kolter R, Losick R, Guo JH (2013) Biocontrol of tomato wilt disease by Bacillus subtilis isolates from natural environments depends on conserved genes mediating biofilm formation. Environ Microbiol 15(3):848–864. doi:10.1111/j.1462-2920.2012.02860.x

  9. Cho KM, Math RK, Hong SY, Asraful Islam SM, Mandanna DK, Cho JJ, Yun MG, Kim JM, Yun HD (2009) Iturin produced by Bacillus pumilus HY1 from Korean soybean sauce (kanjang) inhibits growth of aflatoxin producing fungi. Food Control 20(4):402–406. doi:10.1016/j.foodcont.2008.07.010

  10. Comella N, Grossman AD (2005) Conservation of genes and processes controlled by the quorum response in bacteria: characterization of genes controlled by the quorum-sensing transcription factor ComA in Bacillus subtilis. Mol Microbiol 57(4):1159–1174. doi:10.1111/j.1365-2958.2005.04749.x

  11. Coutte F, Leclere V, Bechet M, Guez JS, Lecouturier D, Chollet-Imbert M, Dhulster P, Jacques P (2010) Effect of pps disruption and constitutive expression of srfA on surfactin productivity, spreading and antagonistic properties of Bacillus subtilis 168 derivatives. J Appl Microbiol 109(2):480–491. doi:10.1111/j.1365-2672.2010.04683.x

  12. Coutte F, Niehren J, Dhali D, John M, Versari C, Jacques P (2015) Modeling leucine’s metabolic pathway and knockout prediction improving the production of surfactin, a biosurfactant from Bacillus subtilis. Biotechnol J 10(8):1216–1234. doi:10.1002/biot.201400541

  13. Das P, Mukherjee S, Sen R (2008) Antimicrobial potential of a lipopeptide biosurfactant derived from a marine Bacillus circulans. J Appl Microbiol 104(6):1675–1184. doi:10.1111/j.1365-2672.2007.03701.x

  14. Dehghan-Noude G, Housaindokht M, Bazzaz BS (2005) Isolation, characterization, and investigation of surface and hemolytic activities of a lipopeptide biosurfactant produced by Bacillus subtilis ATCC 6633. J Microbiol 43(3):272–276

  15. Deleu M, Lorent J, Lins L, Brasseur R, Braun N, El Kirat K, Nylander T, Dufrêne YF, Mingeot-Leclercq M-P (2013) Effects of surfactin on membrane models displaying lipid phase separation. BBA - Biomembranes 1828(2):801–815. doi:10.1016/j.bbamem.2012.11.007

  16. Deleu M, Paquot M, Nylander T (2005) Fengycin interaction with lipid monolayers at the air-aqueous interface-implications for the effect of fengycin on biological membranes. J Colloid Interface Sci 283(2):358–365. doi:10.1016/j.jcis.2004.09.036

  17. Dey G, Bharti R, Dhanarajan G, Das S, Dey KK, Kumar BN, Sen R, Mandal M (2015) Marine lipopeptide iturin A inhibits Akt mediated GSK3beta and FoxO3a signaling and triggers apoptosis in breast cancer. Sci Rep 5:10316. doi:10.1038/srep10316

  18. Gao Z, Zhao X, Lee S, Li J, Liao H, Zhou X, Wu J, Qi G (2013) WH1fungin a surfactin cyclic lipopeptide is a novel oral immunoadjuvant. Vaccine 31(26):2796–2803. doi:10.1016/j.vaccine.2013.04.028

  19. Gao Z, Zhao X, Yang T, Shang J, Shang L, Mai H, Qi G (2014) Immunomodulation therapy of diabetes by oral administration of a surfactin lipopeptide in NOD mice. Vaccine 32(50):6812–6819. doi:10.1016/j.vaccine.2014.08.082

  20. Gonzalez-Jaramillo LM, Aranda FJ, Teruel JA, Villegas-Escobar V, Ortiz A (2017) Antimycotic activity of fengycin C biosurfactant and its interaction with phosphatidylcholine model membranes. Colloids Surf B Biointerfaces 156:114–122. doi:10.1016/j.colsurfb.2017.05.021

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

  22. Gudiña EJ, Rangarajan V, Sen R, Rodrigues LR (2013) Potential therapeutic applications of biosurfactants. Trends Pharmacol Sci 34(12):667–675. doi:10.1016/

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

  24. Han Q, Wu F, Wang X, Qi H, Shi L, Ren A, Liu Q, Zhao M, Tang C (2015) The bacterial lipopeptide iturins induce Verticillium dahliae cell death by affecting fungal signalling pathways and mediate plant defence responses involved in pathogen-associated molecular pattern-triggered immunity. Environ Microbiol 17(4):1166–1188. doi:10.1111/1462-2920.12538

  25. Han Y, Huang X, Cao M, Wang Y (2008) Micellization of surfactin and its effect on the aggregate conformation of amyloid beta (1-40). J Phys Chem B 112(47):15195–15201. doi:10.1021/jp805966x

  26. Huang X, Lu Z, Zhao H, Bie X, Lü FX, Yang S (2006) Antiviral activity of antimicrobial lipopeptide from Bacillus subtilis fmbj against Pseudorabies virus, Porcine Parvovirus, Newcastle Disease virus and Infectious Bursal Disease virus in vitro. Int J Pept Res Ther 12(4):373–377. doi:10.1007/s10989-006-9041-4

  27. Hwang MH, Lim JH, Yun HI, Rhee MH, Cho JY, Hsu WH, Park SC (2005) Surfactin C inhibits the lipopolysaccharide-induced transcription of interleukin-1beta and inducible nitric oxide synthase and nitric oxide production in murine RAW 264.7 cells. Biotechnol Lett 27(20):1605–1608. doi:10.1007/s10529-005-2515-1

  28. Hwang YH, Kim MS, Song IB, Park BK, Lim JH, Park SC, Yun HI (2009) Subacute (28 day) toxicity of surfactin C, a lipopeptide produced by Bacillus subtilis, in rats. J Health Sci 55(3):351–355. doi:10.1248/jhs.55.351

  29. Ines M, Dhouha G (2015) Lipopeptide surfactants: production, recovery and pore forming capacity. Peptides 71:100–112. doi:10.1016/j.peptides.2015.07.006

  30. Jauregi P, Coutte F, Catiau L, Lecouturier D, Jacques P (2013) Micelle size characterization of lipopeptides produced by B. subtilis and their recovery by the two-step ultrafiltration process. Sep Purif Technol 104:175–182. doi:10.1016/j.seppur.2012.11.017

  31. Jiang C, Shi J, Liu Y, Zhu C (2014) Inhibition of Aspergillus carbonarius and fungal contamination in table grapes using Bacillus subtilis. Food Control 35(1):41–48. doi:10.1016/j.foodcont.2013.06.054

  32. Jiao S, Li X, Yu HM, Yang H, Li X, Shen ZY (2017) In situ enhancement of surfactin biosynthesis in Bacillus subtilis using novel artificial inducible promoters. Biotechnol Bioeng 114(4):832–842. doi:10.1002/bit.26197

  33. Kaneda M, Kajimura Y (2003) New antifungal antibiotics, bacillopeptins and fusaricidins. ChemInform 122(3):651–671. doi:10.1248/yakushi.122.651

  34. Kikuchi T, Hasumi K (2002) Enhancement of plasminogen activation by surfactin C: augmentation of fibrinolysis in vitro and in vivo. BBA-Proteins Proteom 1596(2):234–245. doi:10.1016/S0167-4838(02)00221-2

  35. Kikuchi T, Hasumi K (2003) Enhancement of reciprocal activation of prourokinase and plasminogen by the bacterial lipopeptide surfactins and iturin Cs. J Antibiot (Tokyo) 56(1):34–37. doi:10.7164/antibiotics.56.34

  36. Kim K, Jung SY, Lee DK, Jung JK, Park JK, Kim DK, Lee CH (1998) Suppression of inflammatory responses by surfactin, a selective inhibitor of platelet cytosolic phospholipase A(2). Biochem Pharmacol 55(7):975–985. doi:10.1016/S0006-2952(97)00613-8

  37. Kim SD, Park SK, Cho JY, Park HJ, Lim JH, Yun HI, Park SC, Lee KY, Kim SK, Rhee MH (2006) Surfactin C inhibits platelet aggregation. J Pharm Pharmacol 58(6):867–870. doi:10.1211/jpp.58.6.0018

  38. Kim SY, Kim JY, Kim SH, Bae HJ, Yi H, Yoon SH, Koo BS, Kwon M, Cho JY, Lee CE, Hong S (2007) Surfactin from Bacillus subtilis displays anti-proliferative effect via apoptosis induction, cell cycle arrest and survival signaling suppression. FEBS Lett 581(5):865–871. doi:10.1016/j.febslet.2007.01.059

  39. Koglin A, Lohr F, Bernhard F, Rogov VV, Frueh DP, Strieter ER, Mofid MR, Guntert P, Wagner G, Walsh CT, Marahiel MA, Dotsch V (2008) Structural basis for the selectivity of the external thioesterase of the surfactin synthetase. Nature 454(7206):907–911. doi:10.1038/nature07161

  40. Kracht M, Rokos H, Ozel M, Kowall M, Pauli G, Vater J (1999) Antiviral and hemolytic activities of surfactin isoforms and their methyl ester derivatives. J Antibiot 52(7):613–619. doi:10.7164/antibiotics.52.613

  41. Lee JH, Nam SH, Seo WT, Yun HD, Hong SY, Kim MK, Cho KM (2012) The production of surfactin during the fermentation of cheonggukjang by potential probiotic Bacillus subtilis CSY191 and the resultant growth suppression of MCF-7 human breast cancer cells. Food Chem 131(4):1347–1354. doi:10.1016/j.foodchem.2011.09.133

  42. Lim JH, Park BK, Kim MS, Hwang MH, Rhee MH, Park SC, Yun HI (2005) The anti-thrombotic activity of surfactins. J Vet Sci 6(4):353–355

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

  44. Meena KR, Kanwar SS (2015) Lipopeptides as the antifungal and antibacterial agents: applications in food safety and therapeutics. Biomed Res Int 2015(3):1–9. doi:10.1155/2015/473050

  45. Mizumoto S, Hirai M, Shoda M (2006) Production of lipopeptide antibiotic iturin A using soybean curd residue cultivated with Bacillus subtilis in solid-state fermentation. Appl Microbiol Biotechnol 72(5):869–875. doi:10.1007/s00253-006-0389-3

  46. Myoungseok K, Jonghwan L, Byungkwon P, Yunhwan H, Song IB, Seungchun P, Yun HI (2009) Effect of surfactin on growth performance of weaning piglets in combination with Bacillus subtilis BC1212, vol 26,

  47. Nasir MN, Besson F (2012) Interactions of the antifungal mycosubtilin with ergosterol-containing interfacial monolayers. BBA-Biomembranes 1818(5):1302–1308. doi:10.1016/j.bbamem.2012.01.020

  48. Ongena M, Jacques P (2008) Bacillus lipopeptides: versatile weapons for plant disease biocontrol. Trends Microbiol 16(3):115–125. doi:10.1016/j.tim.2007.12.009

  49. Ongena M, Jourdan E, Adam A, Paquot M, Brans A, Joris B, Arpigny JL, Thonart P (2007) Surfactin and fengycin lipopeptides of Bacillus subtilis as elicitors of induced systemic resistance in plants. Environ Microbiol 9(4):1084–1090. doi:10.1111/j.1462-2920.2006.01202.x

  50. Ostroumova OS, Malev VV, Ilin MG, Schagina LV (2010) Surfactin activity depends on the membrane dipole potential. Langmuir 26(19):15092–15097. doi:10.1021/la102691y

  51. Palanisamy P, Raichur AM (2008) Biosurfactant mediated synthesis of NiO nanorods. Mater Lett 62(4–5):743–746. doi:10.1016/j.matlet.2007.06.053

  52. Pan H, Zhao X, Gao Z, Qi G (2014) A surfactin lipopeptide adjuvanted hepatitis B vaccines elicit enhanced humoral and cellular immune responses in mice. Protein Peptide Lett 21(9):901–910. doi:10.2174/0929866521666140418100743

  53. Park SY, Kim JH, Lee SJ, Kim Y (2013a) Involvement of PKA and HO-1 signaling in anti-inflammatory effects of surfactin in BV-2 microglial cells. Toxicol Appl Pharmacol 268(1):68–78. doi:10.1016/j.taap.2013.01.017

  54. Park SY, Kim JH, Lee SJ, Kim Y (2013b) Surfactin exhibits neuroprotective effects by inhibiting amyloid beta-mediated microglial activation. Neurotoxicology 38:115–123. doi:10.1016/j.neuro.2013.07.004

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

  56. Park SY, Kim Y (2009) Surfactin inhibits immunostimulatory function of macrophages through blocking NK-kappaB, MAPK and Akt pathway. Int Immunopharmacol 9(7–8):886–893. doi:10.1016/j.intimp.2009.03.013

  57. Peypoux F, Bonmatin JM, Wallach J (1999) Recent trends in the biochemistry of surfactin. Appl Microbiol Biot 51(5):553–563. doi:10.1007/s002530051432

  58. Qi G, Zhu F, Du P, Yang X, Qiu D, Yu Z, Chen J, Zhao X (2010) Lipopeptide induces apoptosis in fungal cells by a mitochondria-dependent pathway. Peptides 31(11):1978–1986. doi:10.1016/j.peptides.2010.08.003

  59. Rodrigues L, Banat IM, Teixeira J, Oliveira R (2006) Biosurfactants: potential applications in medicine. J Antimicrob Chemother 57(4):609–618. doi:10.1093/jac/dkl024

  60. Sahnoun R, Mnif I, Fetoui H, Gdoura R, Chaabouni K, Makni-Ayadi F, Kallel C, Ellouze-Chaabouni S, Ghribi D (2014) Evaluation of Bacillus subtilis SPB1 lipopeptide biosurfactant toxicity towards mice. Int J Pept Res Ther 20(3):333–340. doi:10.1007/s10989-014-9400-5

  61. Schneider J, Taraz K, Budzikiewicz H, Deleu M, Thonart P, Jacques P (2012) The structure of two fengycins from Bacillus subtilis S499. Z Naturforsch C 54(11):859–865. doi:10.1515/znc-1999-1102

  62. Stein T (2005) Bacillus subtilis antibiotics: structures, syntheses and specific functions. Mol Microbiol 56(4):845–857. doi:10.1111/j.1365-2958.2005.04587.x

  63. Tang Q, Bie X, Lu Z, Lv F, Tao Y, Qu X (2014) Effects of fengycin from Bacillus subtilis fmbJ on apoptosis and necrosis in Rhizopus stolonifer. J Microbiol 52(8):675–680. doi:10.1007/s12275-014-3605-3

  64. Vollenbroich D, Ozel M, Vater J, Kamp RM, Pauli G (1997) Mechanism of inactivation of enveloped viruses by the biosurfactant surfactin from Bacillus subtilis. Biologicals 25(3):289–297. doi:10.1006/biol.1997.0099

  65. Wang X, Hu W, Zhu L, Yang Q (2017) Bacillus subtilis and surfactin inhibit the transmissible gastroenteritis virus from entering the intestinal epithelial cells. Biosci Rep 37(2):BSR20170082. doi:10.1042/bsr20170082

  66. Xu HM, Rong YJ, Zhao MX, Song B, Chi ZM (2014) Antibacterial activity of the lipopetides produced by Bacillus amyloliquefaciens M1 against multidrug-resistant Vibrio spp. isolated from diseased marine animals. Appl Microbiol Biotechnol 98(1):127–136. doi:10.1007/s00253-013-5291-1

  67. Yin HP, Guo CL, Wang Y, Liu D, Lv YB, Lv FX, Lu ZX (2013) Fengycin inhibits the growth of the human lung cancer cell line 95D through reactive oxygen species production and mitochondria-dependent apoptosis. Anti-Cancer Drug 24(6):587–598. doi:10.1097/CAD.0b013e3283611395

  68. Zeriouh H, Romero D, Garcia-Gutierrez L, Cazorla FM, de Vicente A, Perez-Garcia A (2011) The iturin-like lipopeptides are essential components in the biological control arsenal of Bacillus subtilis against bacterial diseases of cucurbits. Mol Plant-Microbe Interact 24(12):1540–1552. doi:10.1094/MPMI-06-11-0162

  69. Zhang B, Dong C, Shang Q, Han Y, Li P (2013) New insights into membrane-active action in plasma membrane of fungal hyphae by the lipopeptide antibiotic bacillomycin L. BBA-Biomembranes 1828(9):2230–2237. doi:10.1016/j.bbamem.2013.05.033

  70. Zhang L, Xing X, Ding J, Zhao X, Qi G (2017) Surfactin variants for intra-intestinal delivery of insulin. Eur J Pharm Biopharm 115:218–228. doi:10.1016/j.ejpb.2017.03.005

  71. Zhang Y, Liu C, Dong B, Ma X, Hou L, Cao X, Wang C (2015) Anti-inflammatory activity and mechanism of surfactin in lipopolysaccharide-activated macrophages. Inflammation 38(2):756–764. doi:10.1007/s10753-014-9986-y

  72. Zhu Z, Zhang G, Luo Y, Ran W, Shen Q (2012) Production of lipopeptides by Bacillus amyloliquefaciens XZ-173 in solid state fermentation using soybean flour and rice straw as the substrate. Bioresour Technol 112:254–260. doi:10.1016/j.biortech.2012.02.057

Download references


This review was supported by the National Science-Technology Support Plan Projects (No. 2015BAD16B02), the National Natural Science Fund (Grant No. 31471718), the Agriculture Department of China (Grant No. CARS-30), and the Northwestern Polytechnical University (No. 3102014JCQ15011 and No. 3102014GEKY1010).

Author information

Haobin Zhao and Junling Shi were responsible for writing the review. Muhammad Shahid Riaz Rajoka assisted in revising the article. Dongyan Shao and Chunming Jiang assisted in providing references for the manuscript. Qi Li, Qinsheng Huang, Hui Yang, and Mingliang Jin did the final proofreading of the manuscript. All authors reviewed the manuscript.

Correspondence to Junling Shi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation


  • Bacillus subtilis
  • Lipopeptide
  • Surfactin
  • Iturin
  • Fengycin