Surfactants tailored by the class Actinobacteria

23 Pages·2015·1.57 MB·English

by  Johannes H. Kügler

REVIEW
published:19March2015
doi:10.3389/fmicb.2015.00212
Surfactants tailored by the class
Actinobacteria
JohannesH.Kügler1*,MarilizeLeRoes-Hill2,ChristophSyldatk1andRudolfHausmann3
1TechnicalBiology,InstituteofProcessEngineeringinLifeSciences,KarlsruheInstituteofTechnology,Karlsruhe,Germany,
2BiocatalysisandTechnicalBiologyResearchGroup,InstituteofBiomedicalandMicrobialBiotechnology,CapePeninsula
UniversityofTechnology,Bellville,SouthAfrica,3BioprocessEngineering,InstituteofFoodScienceandBiotechnology,
UniversityofHohenheim,Stuttgart,Germany
Globally the change towards the establishment of a bio-based economy has resulted
in an increased need for bio-based applications. This, in turn, has served as a
driving force for the discovery and application of novel biosurfactants. The class
Actinobacteria represents a vast group of microorganisms with the ability to produce
a diverse range of secondary metabolites, including surfactants. Understanding the
extensive nature of the biosurfactants produced by actinobacterial strains can assist
in finding novel biosurfactants with new potential applications. This review therefore
presents a comprehensive overview of the knowledge available on actinobacterial
surfactants, the chemical structures that have been completely or partly elucidated,
Editedby:
PattanathuK.S.M.Rahman, as well as the identity of the biosurfactant-producing strains. Producer strains of
TeessideUniversity,UK not yet elucidated compounds are discussed, as well as the original habitats of
Reviewedby: all the producer strains, which seems to indicate that biosurfactant production
ToruMatsui,
is environmentally driven. Methodology applied in the isolation, purification and
UniversityoftheRyukyus,Japan
WaelIsmail, structural elucidation of the different types of surface active compounds, as well as
ArabianGulfUniversity,Bahrain
surfactant activity tests, are also discussed. Overall, actinobacterial surfactants can
*Correspondence:
be summarized to include the dominantly occurring trehalose-comprising surfactants,
JohannesH.Kügler,
SectionII:TechnicalBiology,Institute othernon-trehalosecontainingglycolipids,lipopeptidesandthemorerareactinobacterial
ofProcessEngineeringinLife surfactants. The lack of structural information on a large proportion of actinobacterial
Sciences,KarlsruheInstituteof
surfactants should be considered as a driving force to further explore the abundance
Technology,Engler-Bunte-Ring1,
76131Karlsruhe,Germany and diversity of these compounds. This would allow for a better understanding
[email protected]
of actinobacterial surface active compounds and their potential for biotechnological
application.
Specialtysection:
Thisarticlewassubmittedto
Keywords:biosurfactant,emulsifier,glycolipid,lipopeptide,trehaloselipid,Rhodococcus,rhamnolipid
Microbiotechnology,Ecotoxicology
andBioremediation,asectionofthe
journalFrontiersinMicrobiology
Microbial Surfactants and their Applications
Received:23January2015
Accepted:02March2015
Microbially derived compounds that share hydrophilic and hydrophobic moieties, and that
Published:19March2015
are surface active, are commonly referred to as biosurfactants. Many have been detected and
Citation: described, and the majorityare molecules of low molecular weight. Within this group of low
KüglerJH,LeRoes-HillM,SyldatkC
molecular weight microbial surfactants, the classes of lipopeptides or glycolipids, where fatty
andHausmannR (2015)Surfactants
acid or hydroxy fatty acid chains are linked to either peptides or carbohydrates, have been
tailoredbytheclassActinobacteria.
Front.Microbiol.6:212. extensively studied (Hausmann and Syldatk, 2014). The combinations of different types of
doi:10.3389/fmicb.2015.00212 hydrophilicandhydrophobicmoietieswithinsurfactantsareinnumerableandhighlybiodiverse.
FrontiersinMicrobiology|www.frontiersin.org 1 March2015|Volume6|Article212
Kügleretal. SurfactantstailoredbytheclassActinobacteria
Duetotheiramphiphillicstructures,surfactantsactasemulsify- Other promising studies for the potential application of acti-
ingagents,resultinginlowsurfacetensionsofinterphases.Often, nobacterialbiosurfactantsareinenvironmentalapplicationssuch
microorganisms produce them when growing on hydrophobic asbioremediation:Oilspillsweresuccessfullydispersedbybio-
carbonsourcesorwhenexposedtogrowthlimitingconditions. surfactants produced by a Gordonia sp. (Saeki et al., 2009), a
It is hypothesized, that biosurfactants play a role in the uptake Dietziasp.(Wangetal.,2014)andaRhodococcussp.(Kuyukina
of various hydrophobic carbon sources thus making nutrients and Ivshina, 2010); and trehalose lipids were applied in micro-
bioavailable, as well as the protection of bacteria from harsh bialenhancedoilrecoveryandthecleaningofoilstoragetanks
environmentalconditions(RistauandWagner,1983;Vollbrecht (Franzetti et al., 2010). In medical applications, the production
etal.,1998;Philpetal.,2002).Somebiosurfactantsshowantimi- ofbiosurfactantsaregenerallyconsideredsaferthansynthetically
crobial effects and the distinction of secondary metabolites as produced compounds due to high enzymatic precision during
antibioticsorbiosurfactantsisoftennotstrict. synthesis.Antiproliferationactivitiesofcancerogeniccellscould
Biosurfactants, compared to chemically derived surfactants, be induced by application of various glycolipids (Isoda et al.,
are independent of mineral oil as a feedstock, they are read- 1997;Sudoetal.,2000).Incosmeticapplications,theuseoftre-
ily biodegradable and can be produced at low temperatures. haloselipidsisfavoredabovethatofsodiumdodecylsulfateasit
Furthermore,theyaredescribedtobelesstoxic,effectiveatlow causeslessirritation(Marquesetal.,2009).
concentrations and show effects in bioremediation. Industrial Different types of biosurfactants or bioemulsifiers have been
interestinbiosurfactantsisnotsolelybasedonthebio-acitivityof described to be produced as secondary metabolites within the
thesemolecules,butisalsoduetothebroaderecologicalaware- class Actinobacteria, and to the best of our knowledge, all
nesslinkedtotheirapplication,whichinturnisdrivenbysus- of the producing species belong to the order Actinomycetales
tainability initiatives and green agendas (Marchant and Banat, (Figure1). The following section of the review will focus on
2012).Biosurfactantscanbeappliedinvariousareassuchasthe the different types of actinobacterial biosurfactants reported in
nutrient-,cosmetic-,textile-,varnish-,pharmaceutical-,mining-, literatureaswellastheirkeystructuralfeaturesandbio-activities.
and oil recovery industries (Henkeletal.,2012; Marchant and
Banat,2012;Mülleretal.,2012).
An example of an actinobacterial biosurfactant that has Metabolite Production within the Class
already entered the market and found industrial application, is Actinobacteria
thelipopeptideantibioticdaptomycin.Thisantibioticisusedin
the treatment of diseases caused by Gram positive pathogens Overthepastfewdecades,therehasbeenanincreasedinterest
andhasbeenmarketedasCubicin(cid:13)R byCubistPharmaceuticals. in the discovery of bioactive metabolites with novel bioactive
FIGURE1|Systematic classification of the class Actinobacteria compounds are displayed in numbers. Thirty six surfactant-producing
including subclasses and orders. Suborder, families and genera genera are reported, all belonging to the largest order within the
examined for the production of biosurfactants and bioemulsifying Actinobacteria: Actinomycetales.
FrontiersinMicrobiology|www.frontiersin.org 2 March2015|Volume6|Article212
Kügleretal. SurfactantstailoredbytheclassActinobacteria
properties and their potential for application in medical- or recently identified order Gaiellales has been included (Euzéby,
industrial-based processes. Microbial products are still consid- 2012). Overall, the class Actinobacteria contains five subclasses
eredtobethemostpromisingsourceforthediscoveryofnovel andnineorderswithatotalof54families(Figure1).Thelargest
chemicalsortherapeuticagents(Berdy,2005).Inaddition,vast order, Actinomycetales, is divided into 14 suborders and con-
microbialgeneticresourcesremainsuntappedandcanleadtothe tainsbyfarthehighestdiversitywithintheclassActinobacteria.
developmentofnovelbioactivemetabolites. Itisthereforenotsurprisingthatbiosurfactantsreportedinlit-
In contrast to primary metabolites, secondary metabolites erature focuses on members of this order. The next few para-
often accumulate and have miscellaneous chemical composi- graphs will go into more detail around the different types of
tionsthatarespecies-specific.Thesesecondarymetabolitesoften biosurfactantsthathavebeenidentifiedtobeproducedbyacti-
exhibit bioactivity and are therefore of great interest to vari- nobacterialstrains,theirproduction,purificationandstructural
ousindustries.Themostdominantsourceofmicrobiallyderived elucidation, as well as the clear influence of the environment
bioactivecompoundsisagroupofbacteriaknowntohaverela- the producer organism is found in and their ability to produce
tivelylargegenomesandconstitutesoneofthemainphylawithin biosurfactants.
the Prokaryotes: The class Actinobacteria (Ludwig and Klenk,
2001).TheclassActinobacteriaplayimportantrolesintheenvi- Trehalose-Comprising Glycolipids
ronment,e.g.,nutrientcycling,butalsoincludemajorplant,ani-
malandhumanpathogens(EmbleyandStackebrandt,1994),well The best described biosurfactants amongst the actinobacteria
known examples are the causative agents of leprosy and tuber- areglucose-basedglycolipids,mostofwhichhaveahydrophilic
culosis. Baltz (2008) assumed 5–10% of their genome coding backbone consisting of two α,α-1,1 glycosidic linked glucose
capacity to be used for the production of secondary metabo- units forming a trehalose moiety. Different types of trehalose-
lites and indeed more than 35% of all known bioactive micro- containing glycolipids and their producers have been exten-
bial metabolites and more than 63% of all known prokaryotic sivelyreviewed(AsselineauandAsselineau,1978;Asselineauand
bioactive metabolites arise from actinobacteria (Bérdy, 2012). Lanéelle,1998;Franzettietal.,2010;KuyukinaandIvshina,2010;
Mostsecondarymetaboliteproducersdescribedbelongtofam- Shao,2011;Khanetal.,2012).ThoseoftheclassActinobacteria
iliesoftheActinomycetales,butitisestimatedthatonly∼1%of aremainlyfoundwithinthegeneraRhodococcus,Mycobacterium,
themareculturable(Bérdy,2012).Manyoftheseactinobacterial Nocardia,ArthrobacterandCorynebacterium,andlessfrequently
secondary metabolites exhibit antibacterial, antifungal, antitu- within the genera Tsukamurella, Brevibacterium, and Micrococ-
mor,anticancerand/orcytotoxicproperties(Manivasaganetal., cus (Tables1, 2). Different structures of trehalose lipid com-
2013). Antibiotics, with around 10,000 compounds described prising amphiphilic molecules have been reported: Acyl chains
(Bérdy, 2012) is by far the largest group of metabolites isolated withglycosidiclinkagestoglucoseortrehaloseunitshavebeen
from actinobacteria. Depending on their chemical nature, the reported to vary in number of occurrence, length and type, as
huge number of antibiotic compounds can roughly be classi- well as the position (and number) of their linkage to the sugar
fied into peptides, aminoglycosides, polyketides, alkaloids, fatty ringsandexhibitdifferentcellularfunctions.
acids, and terpenes (Manivasagan et al., 2013; Abdelmohsen For the hydrophobic moiety of trehalose-comprising glycol-
etal.,2014).Besidesantibiotics,otheractinobacterialcompounds ipids, the structures of two main types of trehalose lipids have
describedarebioactivecompoundswithpharmacologicalactivity been elucidated: those carrying a mycolic fatty acid ester and
(pheromones,toxins,enzymeinhibitors,receptorsandimmuno- thosecarryingafattyacidester.
logicalmodulators),withagriculturalactivity(pesticides,herbi- Thesmallest hydrophilicbackbone in glycolipids constitutes
cidesandinsecticides)andotherindustriallyrelevantproperties glucose, the building block of the sugar dimer trehalose. Com-
(pigments and surfactants). Most compounds are derived from pletestructuresofacylglucosescarryingmycolicacidestershave
members of the genus Streptomyces, however, other so-called beenelucidatedandreportedtobeproducedbyisolatesbelong-
“rare”actinomycetesareincreasinglyplayingamoreimportant ingtothegeneraCorynebacteriumandMycobacterium(Brennan
roleintheproductionofbiocompounds(Berdy,2005;Kurtboke, et al., 1970) (Table1), whereas acylglucoses carrying fatty acid
2010). estershavebeendescribedforBrevibacteriumspp.(Okazakietal.,
To fully understand the taxonomic distribution of the acti- 1969)(Table2).
nobacterial strains identified to produce biosurfactants and
bioemulsifying compounds, taxonomic data of the class Acti- TrehaloseLipidMycolicAcidEsters
nobacteria was evaluated. Information were retrieved from the Mycolic acids are long-chain fatty acids and a major compo-
taxonomy browser of the National Center for Biotechnology nentofthecellwallinvariousactinobacteria.Species-dependent,
Information1considering16SrRNAgenesequencebasedreclas- its lengths varies from 22 to 92 carbon atoms; they possess
sifications according to Zhi et al. (2009) and Goodfellow and longβ-hydroxy-α-branchedacylchains,includingcyclopropane
Fiedler(2010).TheorderThermoleophilalesthathasbeenreclas- patterns and oxygenic groups. The synthesis of mycolic acids
sifiedintoanewclass(Euzéby,2013)hasbeenexcludedandthe includescondensationreactions,andtheyarealsoreferredtoas
eumycolicacid,corynemycolicacidandnocardio-mycolicacid,
1National Center for Biotechnology Information (NCBI) Taxonomy
dependingontheirpresenceinMycobacteriumspp.,Corynebac-
Browser. Available online at: http://www.ncbi.nlm.nih.gov/Taxonomy/
terium spp., and Nocardia spp., respectively (Asselineau and
Browser/wwwtax.cgi?mode=Undef&id=201174&lvl=5&lin(accessed01.07.2014-
07.01.2015). Lanéelle,1998).
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Kügleretal. SurfactantstailoredbytheclassActinobacteria
TABLE1|Mycolicandcorynemycoliccontainingtrehaloselipidsthatareofactinobacterialorigin.
Species Strain TLmycolicacidester References
Arthrobacterparaffineus KY4303 TLmycolic(C32–C36) Suzukietal.,1969
Brevibacteriumsp. KY4304/4305 TLmycolic(C32–36) Suzukietal.,1969
Brevibacteriumvitarumen 12143 TLdimycolic(C28–C38) LanéelleandAsselineau,1977
Corynebacteriumdiphtheriae n.a. Glucosemycolic(C32) Brennanetal.,1970
Corynebacteriumspp. KY3543 TLmycolic(C32–36) Suzukietal.,1969
(fasciens,pseudodiphtheriae) KY3541
Corynebacteriummatruchotii ATCC14266 TLdimycolic(C28–C38) DattaandTakayama,1993
Mycobacteriumspp. BCG,n.a. Glucosemycolic(C32) Brennanetal.,1970
(smegmatis,tuberculosis)
Mycobacteriumspp.* Various TLmycolic,dimycolic, Reviewedin:AsselineauandAsselineau,1978;Gautier
(bovis,fortuitum,kansaii,malmoense,phlei, etal.,1992;AsselineauandLanéelle,1998;Vergneand
tuberculosis,smegmatis,szulgai,etc.) Daffé,1998;Dembitsky,2004;Ishikawaetal.,2009;
Shao,2011
Nocardiaspp. n.a. TLmycolic(C32–36) Suzukietal.,1969
Rhodococcusspp.* Various TLmycolic,dimycolic, Reviewedin:AsselineauandAsselineau,1978;Lang
(erythropolis,opacus,ruber,etc.) andPhilp,1998;KuyukinaandIvshina,2010;Shao,
2011;Khanetal.,2012
EXAMPLESOFMYCOLICACIDCONTAININGTREHALOSELIPIDS
1
TrehalosedimycolateproducedbyMycobacteriumtuberculosis
2
TrehalosedicorynemycolateproducedbyRhodococcuserythropolis
*Severalproducingspeciesarereported;TL,trehaloselipid;n.a.,informationnotavailable.
Mycolicacidcomprisingtrehaloselipids(Table1)canbedis- organism hence facilitating the uptake of hydrophobic carbon
tinguished into two different types, the trehalose mycolic lipids sources. The other type, trehalose lipids containing corynemy-
andthetrehalosecorynemycoliclipids.Thesemycobacterialtre- colic acid also carry β-hydroxy-α-branched fatty acid moieties
halosemycolatesordimycolatesarebyfarthemosthydrophobic andhavebeendescribedtooccurwithinthegenusRhodococcus
glycolipids.LinkedtoC6(andC6′)ofthesugarrings,theyvary (2,Table1),carrying30–56carbonatomsandwithinthegenus
amongspeciesinlengthandbranching.Theyareshapedtoform Corynebacterium, carrying 22–36 carbon atoms. They are also
bilayers,implementedintheoutercellwallandusuallynotfound described to occur in mycobacteria (Brennan et al., 1970) and
onthebacterialcellsurface(VergneandDaffé,1998).Trehalose foundintrehaloselipidsofBrevibacteriumvitarumen(Lanéelle
dimycolates (1, Table1), also referred to as “cord factor,” serve and Asselineau, 1977), Arthrobacter paraffineus and a Nocar-
a particular function for the cell. They act as virulence factors dia sp. (Suzuki et al., 1969). Corynemycolic acids are much
and have immuno-modulating activity (Shao, 2011). They may shorter than their mycobacterial counterparts: they lack func-
furtherbeimportanttomaintainahydrophobiccellwallofthe tionalgroupsandareoftenunsaturated.Withinvirulentstrains
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Kügleretal. SurfactantstailoredbytheclassActinobacteria
TABLE2|Trehaloselipidesterofactinobacterialorigin.
Species Strain TLester References
Arthrobactersp. EK1 TLtetraester(C12–C18) Passerietal.,1990
Brevibacteriumthiogenitalis No.653 Glucosediester(C18) Okazakietal.,1969
Micrococcusluteus BN56 TLtetraester(C9–C14) Tulevaetal.,2009
Mycobacteriumspp.* Various TLester Reviewedin:VergneandDaffé,1998;
(africanum,bovis,fortuitum,tuberculosis,etc.) Dembitsky,2004;Shao,2011
Mycobacteriumtuberculosis H37Rv TLsulfolipid Goren,1970;Gilleronetal.,2004
Nocardiafarcinica BN26 TLsuccinictetraester(C7-12) Christovaetal.,2014
Rhodococcusspp.*(erythropolis,longus, Various TLester,TLsuccinicester Reviewedin:AsselineauandAsselineau,1978;
wratislavensis,etc.) LangandPhilp,1998;KuyukinaandIvshina,
2010;Shao,2011;Khanetal.,2012
Tsukamurellapulmonis PCM2578T TLdiester(C18–20/C4–5) Pasciaketal.,2010a
Tsukamurellaspumae DSM44113, TLdiester(C16–18/C4–6) Kügleretal.,2014
Tsukamurellapseudospumae DSM44114
DSM44117
Tsukamurellatyrosinosolvens DSM44370 TLdiester(C16–18/C2–6) Vollbrechtetal.,1998
EXAMPLESOFTREHALOSELIPIDESTERS
3 4
TrehalosediesterproducedbyTsukamurellaspumae SuccinictrehalosetetraesterproducedbyNocardiafarcinia
5
DiacetylatedtrehalosesulfolipidproducedbyMycobacteriumtuberculosis
*Severalproducingspeciesarereported;TL,trehaloselipid.
ofmycobacteria,fivedifferentsulfonatedformsoftrehaloseesters the producing strain. These glycolipid-linked medium chain
havebeenfound,varyingintheiracylationpattern(Khanetal., lengthfattyacidsarefoundwithinthefollowingactinobacterial
2012). genera: Arthrobacter, Brevibacterium, Caseobacter, Micrococcus,
Mycobacterium, Nocardia, Rhodococcus, and Tsukamurella
TrehaloseLipidEsters (Table2).
Actinobacterial trehalose lipid esters are mainly acylated at Anexceptionamongthetrehaloselipidestersdescribed,issul-
C6/C6′oratC2/C3andaresummarizedinTable2.Theamount folipid 1 (Goren, 1970) (5, Table2), a sulfonated and acylated
of hydrophobic chains linked to the trehalose unit varies from trehalose lipid carrying phtio- and hydroxyphtioceranic com-
one to four, forming trehalose mono-, di-, tri- and tetraesters, partments.Theyareknowntocontributetothepathogenesisand
but also octaesters (Singer et al., 1990) (3, Table2). The acyl virulence of Mycobacterium tuberculosis, the causative agent of
chains varies in lengths from C8 to C20, show an unsaturated tuberculosis. Diacyltrehalose sulfate, the biosynthetic precursor
pattern or form short succinoyl acids, giving the trehalose for sulfolipid 1, has recently been isolated from M. tuberculo-
lipid an anionic character (Lang and Philp, 1998; Tokumoto sis (Domenech et al., 2004) and has been used as a target for
et al., 2009) (4, Table2). They are reported to be linked to T-cellmediatedrecognizationandeliminationofM.tuberculosis
the chain length present in hydrophobic carbon source fed to infectedcells(Gilleronetal.,2004).
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Kügleretal. SurfactantstailoredbytheclassActinobacteria
OligosaccharideLipids units,bothcarryingaC6fattyacidmoietyatthethirdsugarunit
Aglycosylatedbackboneoftrehaloseisfoundinoligosaccharide andsuccinicacidatthefirstsugarunit.Somethingthatisrather
lipids (Table3) carrying two to five sugar units. Trisaccharide exceptionalistheacylationpatternatthetrehalosebackbonethat,
lipidsthathavebeenreportedfortheclassActinobacteriaalldif- in its hydrophobic moieties, carries at each unit an acyloxyacyl
ferwithrespecttotheacylationpatternofthethirdglucoseunit. structureintheO-esterlinkagetothecarbohydratewherethe3-
Onesugarofthe1-1′linkeddi-glucosebackboneisfurtherlinked hydroxyC8orC10fattyacidmoietyisfurtheracylatedwithaC6
toathirdsugarunitatC2inthehydrophilicmoeityofoligosac- fattyacid(6,Table3).TheTsukamurellasp.trisaccharidelipids
charidesproducedbyMycobacteriumleprae(Brennan,1989)and areacylatedattwosugarunits,eachcarryingtwoordinaryC8–
Tsukamurellatyrosinosolvens(Vollbrechtetal.,1998).Thethird C10 fatty acid units. Furthermore, a tetrasaccharide lipid form
sugarunitislinkedatC3inaterrestrialactinomycetereported ofthisglycolipidhasalsobeenfoundtooccur(Vollbrechtetal.,
by Esch et al. (1999) and at C4 in a Rhodococcus sp. (Konishi 1998)(7,Table3).
et al., 2014) (6, Table3). They also differ with respect to their Non-trehalose based oligosaccharide lipids are found within
hydrophobicnature.Thelattertwoareacylatedatallthreesugar phenol-phtiocerol glycosides in various mycobacteria. These
TABLE3|Actinobacterialoligosaccharidelipids.
Species Strain Oligosaccharidlipids References
Mycobacteriumspp.* Various oligosaccharideester,phenolic Reviewedin:SaadatandBallou,
(avium,kansaii,leprae,linda,malmoense,smegmatis,szulgai, glycolipids 1983;Brennan,1989;
tuberculosis) Dembitsky,2005b
Nocardiacorynebacteroides SM1 Pentasaccharidesuccinicoctaester Powallaetal.,1989
(C2–C8)
Rhodococcussp. NBRC1097287 Trisaccharidsuccinictetraester Konishietal.,2014
Rhodococcusfascians NBRC12155 (C8-O-C6/C6)
Tsukamurellatyrosinosolvens DSM44370 Tri/tetrasaccharideester(C8-10) Vollbrechtetal.,1998
EXAMPLESOFOLIGOSACCHARIDELIPIDS
6 7
SuccinictrisaccharidelipidproducedbyRhodococcusfascians TetrasaccharidelipidproducedbyTsukamurellatyrosinosolvens
8
Methylateddirhamnose/glucosephenolphtiocerolnamedphenolicglycolipidIofMycobacteriumlepraeBrennan,1989
*Severalproducingstrainsarereported.
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Kügleretal. SurfactantstailoredbytheclassActinobacteria
oligosaccharidelipids,alsotermedphenolicglycolipids,contain salonariumChristovaetal.,2004,andaNocardioidessp.Vasileva-
tri-andtetraglycosylunitscomposedofvariousmethylatedsug- TonkovaandGesheva,2005)(Table11).
ars that are mainly based on rhamnose and partly on fucose, A different group of glycolipids are lipidic structures based
glucoseandarabinose(Brennan,1989).Therarelydescribedphe- on dimannose. Typically they are linked via a glycerol unit
nolicacylationpatternisboundtodimycocerosylphtiocerolacyl to different numbers of fatty acid chains. They have been
groups.ThephenolicglycolipidIofM.lepraecarriesthreemyco- reviewed in Shaw (1970) and structures have been identified
cerosylacylgroupseachinlengthofC30–C34(Brennan,1989) forcompoundsproducedbyspeciesbelongingtotheactinobac-
(8,Table3). terial genera Micrococcus (Lennarz and Talamo, 1966), Curto-
Inindustrialandenvironmentalprocessesthepotentialoftre- bacterium(Mordarskaetal.,1992),Saccharopolyspora(Gamian
haloselipidscouldbecomevaluableastheyhaveshowninterest- et al., 1996), Rothia (Pasciak et al., 2002, 2004), Nocardiop-
ing properties in several studies that focus on the remediation sis (Pasciak et al., 2004), Arthrobacter (Pasciak et al., 2010b)
of hydrocarbon contaminated soils, the removal of suspended as well as the strain Sinomonas atrocyaneus (Niepel et al.,
solidsfromwastewater(Franzettietal.,2010)andinenhancedoil 1997),formerlyclassifiedasArthrobacteratrocyaneus.Thesedi-
recovery(Christofi andIvshina,2002).However,mostresearch mannose based glycolipids are composed of hydrophilic α-D-
arecenteredaroundthebio-activityoftrehaloselipidmolecules mannopyranosedimerslinkedwithtwoC14–C16isooranteiso
thatexhibitbiomedicalpropertiessuchasantimicrobial,antiviral fatty acid chains. One chain is directly esterified to the C6
(Azumaetal.,1987;Watanabeetal.,1999;Shao,2011)andanti- hydroxyl group of one sugar unit, while the second fatty acid
tumoractivities(Sudoetal.,2000;Franzettietal.,2010;Gudiña chain is linked via a glycerol moiety to the C3 of the same
etal.,2013).Duetotheirfunctionsincellmembraneinteractions sugar unit. The glycerol moiety is monoacylated at either the
they can act as therapeutic agents (Zaragoza et al., 2009; Shao, primary or secondary methylene position (9, Table4) and its
2011)orhaveanimpactonthepathogenesisofcausativeagents acylation site can be used to distinguish taxonomic proper-
ofinfections,suchasthosecausedbypathogenicM.tuberculo- ties of the different producer strains. These compounds have
sis,Corynebacteriumdiphteriae,andtheopportunisticpathogens, been isolated intracellularly and they act as precursors and cell
Mycobacterium avium, Mycobacterium intracellulare, Nocardia membrane anchors for the synthesis of lipoarabinomannan, a
asteroides, Corynebacterium matruchotii, and Corynebacterium polymeric surfactant and actinobacterial cell wall component
xerosis (Kuyukina and Ivshina, 2010). Trehalose lipids can be (PakkiriandWaechter,2005)(seesectiononpolymericbiosur-
excretedintothecultivationsupernatantorcanbeproducedas factants).
non-covalently linked lipids bound to the cell wall or they can The coexistence of galactosyl diglycerides (10, Table4) in
becellwallintegratedthusposinglimitstoquantitiesproduced Arthrobacter scleromae and Arthrobacter globiformis (Pasciak
bytheorganisms,adisadvantageforitspotentialexploitationin et al., 2010b) have been described and can be used as a gly-
largescaleproductionprocesses. comarker to distinguish these strains from the opportunistic
pathogens,RothiamucilaginosaandRothiadentocariosa(Pasciak
Non-Trehalose Glyolipids etal.,2002,2004).
Hexose-ComprisingGlycolipids MacrocyclicGlycosides
Besides the trehalose-containing biosurfactants and its con- Among the biosurfactants produced by actinobacteria, macro-
geners,severalglycolipidshavebeenelucidatedthatareproduced cyclicglycosides(Table5)andmacrocylcicdilactones(Table6)
byactinobacteriaandshareotherhydrophilicmoieties.Bysimply canbedistinguishedandareoftenknowntoexhibitbio-activity
varyingthecarbonsourceinthegrowthmediafromn-alkanesto againstarangeoforganisms.Thealiphaticmacrolideantibiotic,
eithersucroseorfructose,thehydrophilicpartofthesurfactant brasilinolide, is produced by Nocardia brasiliensis and exhibits
producedwasreportedtobeswitchedfromtrehalosetofructose both antifungal and antibacterial activity. Three different vari-
bymembersofthegenusArthrobacter,Corynebacterium,Nocar- ants havebeen described by Tanaka et al.(1997),Mikami et al.
dia,Brevibacterium,andMycobacterium(ItohandSuzuki,1974) (2000)andKomatsuetal.(2004).AllconsistofaC32-membered
andsucroseinthecaseofthesamegeneraexceptMycobacterium macrolidewithasugarmoietybutdifferwithregardstotheacy-
(Suzukietal.,1974).Compoundsforwhichstructureshavebeen lation site of a malonic acid ester side chain (11, Table5). The
elucidatedarelistedinTable4. C16-membered dimeric macrolide elaiophylin and its variants
Besides the rhamnose-containing phenolic glycolipids men- havebeenisolatedfromvariousStreptomycesspp.includinghigh
tioned in the oligosaccharide lipid section, the occurrence of producerstrains.Itexhibitsbio-activepropertiesagainstintesti-
other rhamnose-based lipids have recently been detected in a nalwormsaswellasantimicrobial,antitumorandimmunosup-
deep sea isolate identified as Dietzia maris (Wang et al., 2014) pressantactivities.Aputative95kbpbiosyntheticgeneclusterof
andhasbeenidentifiedasaC10:C10di-rhamnolipid.Thisrepre- elaiophylinhasbeenproposed(Haydocketal.,2004).Dembitsky
sentsauniqueoccurrencewithintheclassActinobacteria.Other (2005a,c)reviewedthedifferenttypesofC14-memberedlactam
rhamnolipid producing actinobacteria are admittedly declared ringsthatareattachedtoanaminosugar(12,Table5).Fluvirucin
as producing strains in literature, however the surface active hasbeenisolatedfromvariousActinomaduraspp.,Streptomyces
compounds produced have either not been elucidated or iden- spp., Microtetraspora spp., and Saccharotrix mutabilis. The dif-
tified as rhamnolipids with debatable structural characteriza- ferent fluvirucins share a common lactam ring unit but differ
tions(RhodoccocusfasciansGeshevaetal.,2010,Renibacterium in terms of glycosylation. All of them act as potent antifungal
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TABLE4|Non-trehalosecomprisingglycolipidsproducedbyactinobacteria.
Species Strain Hexoselipids References
Arthrobacterparaffineus KY4303 Sucrosemycolic(C32–C36)* Suzukietal.,1974
Arthrobacterparaffineus KY4303 Fructosecoryne-anddicorynemycolic* ItohandSuzuki,1974
Arthrobacterspp. ATCC8010T Dimannosylacyl(C15–C17)monoglyceride(C15–C17) Pasciaketal.,2010b
(globiformis,scleromae) YH2001T Galactosyldiglyceride(C15–C17)
Brevibacteriumbutanicum KY4332 Fructosecoryne-anddicorynemycolic* ItohandSuzuki,1974
Brevibacteriumspp. n.a. Sucrosemycolic(C32–C36)* Suzukietal.,1974
Corynebacteriumspp. n.a. Sucrosemycolic(C32–C36)* Suzukietal.,1974
Corynebacteriumspp. n.a. Fructosecoryne-anddicorynemycolic* ItohandSuzuki,1974
Curtobacteriumflaccumfaciens ATCC13437 Di-andtrimannosylglyceride(C18–C19cyclopropane) Mordarskaetal.,1992
Dietziamaris MCCC1A00160 Rhamnolipid(C10/C10) Wangetal.,2014
Micrococcuslysodeikticus ATCC4698 Dimannosylglyceride(C14) LennarzandTalamo,1966
Mycobacteriumavium KY3844 Fructosecoryne-anddicorynemycolic* ItohandSuzuki,1974
Mycobacteriumkoda KY3852
Nocardiabutanica KY4333 Sucrosemycolic(C32–C36)* Suzukietal.,1974
Nocardiaconvulutus KY3907
Nocardiarubra KY3844 Fructosecoryne-anddicorynemycolic* ItohandSuzuki,1974
Nocardiabutanica KY4333
Nocardiaconvulutus KY3907
Nocardiopsisdassonvillei PCM2492T(ATCC23218) Dimannosylacyl(C15)monoglyceride(C16) Pasciaketal.,2004
Rothiadentocariosa PCM2249T(ATCC17931) Dimannosylacylmonoglyceride(C16–C19) Mordarskaetal.,1992;
Pasciaketal.,2002
Rothiamucilaginosa PCM2415T(ATCC25296T) Dimannosylacyl(C15)monoglyceride(C16) Pasciaketal.,2004
Saccharopolysporaspp. ATCC27875T Dimannosylacyl(C15–C16)monoglyceride(C16) Gamianetal.,1996;
(erythraea,hirsuta,rectivirgula,sp.) ATCC11635T Pasciaketal.,2002,2004
IMRU1258
LL-100-46)
Sinomonasartrocyaneus LMG3814T Dimannoseylacyl(C14)monoglyceride(C16) Niepeletal.,1997
EXAMPLESOFNON-TREHALOSECOMPRISINGHEXOSELIPIDS
9 10
DimannosylacylmonoglycerideproducedbyRothiamucilaginosa GalactosyldiglycerideproducedbyArthorbacterglobiformisandArthrobacterscleromae
n.a.,noinformationavailable;*Sucroseandfructosebasedsurfactantsarevariantsoftrehaloselipids.
agentsagainstCandidaspp.andshowantiviralpropertiesagainst Table6).GlucolypsinvariantswithC18andC17fattyacidchains
influenzaAvirus(Dembitsky,2005c). ofthesametypealsooccur.Glycolypsinisreportedtoincrease
Among the macrocyclic dilactones, glucolypsin, an acylglu- the activity of glucokinases by relieving its inhibition via long
cosedimerhasbeenisolatedfromStreptomycespurpurogeniscle- chainfattyacylCoAesters(Qian-Cutroneetal.,1999).Derivates
roticusandNocardiavacciniibyQian-Cutroneetal.(1999).This ofglucolypsinthatshareacommonbackbone,havebeenshown
extraordinaryglycolipidisformedoutoftwoglucoseunitslinked toexhibitantiviralandantibioticproperties.Incontrasttoglu-
toidenticaliso-branchedC18acylchainsthateachcarryamethyl colypsin, the acylglucose dimer of fattiviracins (C24/C26) and
groupatC2andahydroxylgroupatC3oftheacylchain.Bycon- cycloviracins (C24/C33) are built up out of trihydroxy fatty
nectingtheC6′oftheglucosemoleculetothecarboxy-C1ofthe acids, each of them glycosidic linked to a further glucose unit
fatty acid chain, a rotationally symmetric dimer is formed (13, at the third hydroxyl group. Cycloviracins are characterized by
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TABLE5|Macrocyclicglycosidesproducedbyactinobacteria.
Species Strain Macrocyclicglycoside References
Actinomaduraspp.* Various Fluvirucin(14Cmacrolide) Reviewedin:Dembitsky,
(roseorufaroseorura,vulgaris,yumaensis) 2005a,c
Microtetrasporapusilla R359-5 FluvirucinB1(14Cmacrolide) Dembitsky,2005a
Microtetrasporatyrrheni Q464-31 Fluvirucins(14Cmacrolide) Dembitsky,2005a,c
Nocardiabrasiliensis IFM0406 BrasilinolideA,B,C Tanakaetal.,1997;Mikamietal.,
(32Cmacrolide) 2000;Komatsuetal.,2004
Saccharothrixmutabilis R869-9 FluvirucinA2(14Cmacrolide) Dembitsky,2005a
Streptomycesspp.* various Elaiophylinandderivates Reviewedin:Dembitsky,2005a
(antibioticus,erythreus,felleus,hygroscopicus,melanosporus, (16Cmacrolide)
narbonensis,spinichromogenes,violaceoniger) Fluvirucin(14Cmacrolide)
EXAMPLESOFMACROCYCLICGLYCOSIDES
11 12
BrasilinoideAproducedbyNocardiabrasiliensis FluvirucinB1producedbyActinomaduravulgarissubsp.lanata
*Severalproducingstrainsarereported.
afifthglucoseunitboundtotheC26fattyacidchain,thethree et al., 2010) (Table7). Most of them share a backbone of a
non-cyclic sugar units are methoxylated at C2, and the methyl C50 atom carotenoid. They can either be linked to one or
branchesatC2ofthefattyacidmoietiesaremissing.Congeners two hydroxyl groups at the terminal ends (decaprenoxanthin
of fattiviracin are divided into five families according to the and sarcinaxanthin) or one hydroxyl group and one glycosidic
lengthoftheirfattyacidmoietywitheachfamilyshowingsimilar moiety (corynexanthin, decaprenoxanthin monoglycoside and
antiviralactivityagainstherpes,influenzaandhumanimmunod- sarcinaxanthinmonoglycoside).Di-glycosylatedformsarefound
eficiency viruses (Uyeda, 2003). No alterations in the fatty acid within Arthrobacter and Micrococcus (decaprenoxanthin diglu-
chain length of cycloviracins have been reported. Fattiviracins cosideandsarcinaxanthindiglucoside)(17,Table7)andfurther
(14, Table6) have been shown to be produced by Streptomyces exist as an acetylated form at all hydroxyl groups. The terpene
microflavus (Uyeda et al., 1998) and cycloviracins (15, Table6) glycosidesproducedbyRhodococcusrhodochrous,differfromthe
byKibdelosporangiumalbatum(Tsunakawaetal.,1992b). onementionedabove,astheycontainamonocycliccarotenoid
backbone linked to a glucopyranosyl residue at the non-cyclic
end (18, Table7). The glucose unit is further acylated at C6 to
TerpenoidsandTerpeneGlycosides
aC36–C50mycolicacidmoietyleadingtocarotenoidglucoside
Actinobacterialterpenoidandterpeneglycosidesaresummarized
mycolicacidesters.Theseterpeneglycosidesaremainlyfoundin
inTable7.VancoresmycinisaC65highlyoxygenatedterpenoid
pigmentedbacteriaanditishypothesizedthattheyactasantiox-
glycosideproducedbyanAmycolatopsissp.Itcontainsatetramic
idantstoprotectorganismsfrominjuriescausedbyfreeradicals
acid unit and is glycosidic linked to a methylated carbohydrate
(Osawaetal.,2010).
moietycontainingoneaminogroup(16,Table7).Antimicrobial
effect against various bacteria was reported by Hopmann et al. Polymeric Biosurfactants
(2002), most notably against species resistant to the antibiotic
vancomycin(oftenconsideredtobetheantibioticoflastresort The most common polymeric surfactants produced by
forthetreatmentofresistantbacteria).Besidestheterpenoidgly- actinobacteria are macro-amphiphilic lipoglycans such as
coside,severaldifferenttypesofterpeneglycosidesareproduced lipoarabinomannan and its precursors, lipomannan and phos-
byactinobacterialstrains.Theyaresurfactantsthatmostlycarry phatidylinositol mannosides. In contrast to the core of the
terminalhydrophilicgroupslinkedbyahydrophobiccarotenoid actinobacterial cell wall, arabinogalactan and peptidoglycan,
moiety. these polymeric lipoglycans are non-covalently attached to the
Terpeneglycosideshavebeenelucidatedasproductsobtained cell membrane although phosphatidylinositol mannides are
from members of the following genera: Corynebacterium structurally related to lipomannan and lipoarabinomannan
(WeeksandAndrewes,1970),Arthrobacter (Arpinetal.,1972), anchor units. These polymeric glycolipids have been isolated
Rhodococcus (Takaichi et al., 1997), and Micrococcus (Osawa from Mycobacterium spp., Gordonia spp., Rhodococcus spp.,
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TABLE6|Macrocyclicdilactonesproducedbyactinobacteria.
Species Strain Macrocyclicdilactones References
Kibdelosporangiumalbatum ATCC55061 CycloviracinB1andB2(C23/C26) Tsunakawaetal.,1992a,b
Nocardiavaccinii WC65712 GlucolypsinAandB(C19/C19) Qian-Cutroneetal.,1999
Streptomycesmicroflavus No.2445 Fattiviracina1(C22–28/C22–24) Uyedaetal.,1998;Yokomizoetal.,1998
Streptomycespurpurogeniscleroticus WC71634 GlucolypsinAandB(C19/C19) Qian-Cutroneetal.,1999
EXAMPLESOFMACROCYCLICDILACTONES
13
GlucolypsinAproducedbyNocardiavacciniiandStreptomycespurpurogeniscleroticus
14
FattiviracinproducedbyStreptomycesmicroflavus
15
CycloviracinB1producedbyKibdelosporangiumalbatum
Dietzia maris, Tsukamurella paurometabolus, Turicella otitidis, (Briken et al., 2004). Lipoarabinomannans show structural
andAmycolatopsissulphurea(Table8).ExceptforA.sulphurea, similaritytoitsprecursorslipomannanandphosphatidylinositol
allofthesestrainsbelongtothesuborderCorynebacteridaethat mannoside and consist of an α-1,6 linked mannan core with
areknowntocontainmycolicacidsintheircellwall.Itcomprises frequentα-1,2mannosebranchesleadingtoamannanbackbone
thepresenceofmycolicacidsandcontainlipidrichcellenvelope of approximately 20–25 mannose residues substituted with
structures (Sutcliffe, 1997) forming an extremely robust and arabinofuran residues that carry terminal extension motifs,
impermeablecellenvelope(Bergetal.,2007).Lipoarabinoman- whichvaryamongtheproducerspecies(Bergetal.,2007).The
nans are well known to cause immunorepressive functions in lipophilicpartconsistsmainlyofC16glyceridesthatarelinked
diseasessuchastuberculosisandleprosythatarecausedbythe tothemannancorebyaphosphategroup(19,Table8).
pathogenicmycobacterialstrainsM.tuberculosisandM.leprae.
However,non-pathogenicspecieshavealsobeenshowntopro- Lipopeptides
ducelipoarabinomannansandarereportedtohaveanopposite
effectthusstimulatingpro-inflammatoryresponses(Brikenetal., Cyclicandlinearlipopeptidesareproducedbyvariousactinobac-
2004).Themannancoreoflipoarabinomannanandthenumber terialstrainsandaresummarizedinTable9.
of branching units is species dependent. Further differences
in its structure is traced back to capping motifs present at the CyclicLipopeptides
non-reducing termini of the arabinosyl side chains. Mannan Cyclic lipopeptides are the most common type of lipopeptides
caps are mainly present in pathogenic strains, whereas inositol and consist of a peptide chain of various types and numbers
phosphate caps are present in non-pathogenic mycobacteria of amino acids circularized and linked to mainly one fatty acid
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