Mangrove rare actinobacteria

15 Pages·2015·1.64 MB·English

REVIEW
published:20August2015
doi:10.3389/fmicb.2015.00856
Mangrove rare actinobacteria:
taxonomy, natural compound, and
discovery of bioactivity
Adzzie-ShazleenAzman1, IekhsanOthman1, SaraswatiS.Velu1, Kok-GanChan2 and
Learn-HanLee1*
1JeffreyCheahSchoolofMedicineandHealthSciences,MonashUniversitySunwayCampus,Selangor,Malaysia,2Division
ofGeneticsandMolecularBiology,FacultyofScience,InstituteofBiologicalSciences,UniversityofMalaya,KualaLumpur,
Malaysia
Actinobacteria are one of the most important and efficient groups of natural metabolite
producers.ThegenusStreptomyceshavebeenrecognizedasprolificproducersofuseful
naturalcompoundsastheyproducedmorethanhalfofthenaturally-occurringantibiotics
isolated to-date and continue as the primary source of new bioactive compounds.
Editedby:
Lately, Streptomyces groups isolated from different environments produced the same
TziBunNg,
TheChineseUniversityofHongKong, types of compound, possibly due to frequent genetic exchanges between species.
China
As a result, there is a dramatic increase in demand to look for new compounds
Reviewedby: which have pharmacological properties from another group of Actinobacteria, known
PeterPristas,
SlovakAcademyofSciences,Slovakia as rare actinobacteria; which is isolated from special environments such as mangrove.
HenriettaVenter, Recently,mangroveecosystemisbecomingahotspotforstudiesofbioactivitiesandthe
UniversityofSouthAustralia,Australia
discovery of natural products. Many novel compounds discovered from the novel rare
*Correspondence:
actinobacteriahavebeenprovenaspotentialnewdrugsinmedicalandpharmaceutical
Learn-HanLee,
JeffreyCheahSchoolofMedicineand industriessuchasantibiotics,antimicrobials,antibacterials,anticancer,andantifungals.
HealthSciences,MonashUniversity This review article highlights the latest studies on the discovery of natural compounds
Malaysia,JalanLagoonSelatan,
46150BandarSunway,Selangor fromthenovelmangroverareactinobacteriaandprovidesinsightontheimpactofthese
DarulEhsan,Malaysia findings.
[email protected]
Keywords:mangrove,rareactinobacteria,naturalcompounds,bioactivity,drugdiscovery
Specialtysection:
Thisarticlewassubmittedto
Antimicrobials,Resistanceand Introduction
Chemotherapy,
asectionofthejournal Market demand for new drugs is extremely urgent and extensive due to common ailments and
FrontiersinMicrobiology
thefastspreadofdiseases,thedevelopmentofnewdiseaseswithunknowncauses,andthespread
Received:19January2015 ofantibiotic-resistantpathogens(Jiangetal.,2008).Withtheincreasingadvancementinscience
Accepted:06August2015 andtechnology,itispredictedthattherewouldbeagreaterdemandfornewbioactivecompounds
Published:20August2015
synthesizedbyActinobacteriafromvarioussourcesincludingsoilandmarine.
Citation: Mangroveisauniquewoodyplantcommunityofintertidalcoastsintropicalandsubtropical
AzmanA-S,OthmanI,VeluSS,Chan coastal regions. The mangrove forests are among the world’s most productive ecosystems which
K-GandLeeL-H(2015)Mangrove
improves coastal water, produces commercial forest products, supports coastal fisheries, and
rareactinobacteria:taxonomy,natural
protects coastlines. Due to its properties of high salinity, strong winds, extreme tides, high
compound,anddiscoveryof
bioactivity.Front.Microbiol.6:856. temperature,anaerobicsoils,andmuddiness;littleisknownaboutthebacterialcommunityliving
doi:10.3389/fmicb.2015.00856 inthemangroveespeciallyofActinobacteriawiththepotentialtoproducebioactivemetabolites.
FrontiersinMicrobiology|www.frontiersin.org 1 August2015|Volume6|Article856
Azmanetal. Mangroverareactinobacteria
Actinobacteria or Actinomycetes are Gram positive bacteria Microbesconstitutethelargestpoolofmetabolicpathwayson
with high guanine (G) and cytosine (C) rations in their DNA earth with potential biotechnological and environmental
(Goodfellow and Williams, 1983). According to Das et al. implications. In 1988, Alongi reported that in tropical
(2008), the name “Actinomycetes” was derived from two Greek mangroves, 91% of the total microbial biomass is bacteria
words, “atkis” which means ray, and “mykes” which means and fungi, another 7% is algae, and 2% is protozoa (Alongi,
fungus; and it has features of both bacteria and fungi. In 1988).Themicrobialdiversityofmangroveecosystemsprovides
the strict taxonomic sense, Actinobacteria are grouped with informationontheirecologicalroleanduniquebiotechnological
bacteria under the class “Schizomycetes” but limited to the potential in the field of agriculture, industry, medicine, and
order of Actinomycetales (Sivakumar et al., 2005; Gayathri pharmaceuticals(Lageiroetal.,2007).Thebacterialcommunities
and Muralikrishnan, 2013). Actinobacteria can be divided into inmangroveenvironmentswerefirstlydeterminedbyYanetal.
two groups namely, Streptomyces and non-streptomyces or also (2006) and Liang et al. (2007). Both studies used molecular
knownasrareactinobacteria. cloning andsequencing approachestounderstand thediversity
Many studies have found that bioactive compounds of ofprokaryotesintheseenvironments(Andreote,2012).
actinobacteria possess a wide range of biological activities. In The mangrove ecosystem is a largely unexplored source of
the late Twentieth Century, some natural products produced Actinobacteria with the potential to produce active secondary
by Actinobacteria had been used extensively in clinical settings metabolites (Hong et al., 2009). Although several studies
as antibacterials, antifungals, anticancer, antitumor, and on bacterial productivity and activity within the mangrove
antiparasitics (Butler, 2004). It is important to discover new ecosystems were conducted, little is known about their genetic
naturalmetabolitestohandletheproblemofantibiotic-resistant andmetabolicdiversity.
pathogens which are no longer susceptible to the antibiotics
available. However, the recent search for the novel compounds
Metagenomics of Mangrove Microbial
always lead to the rediscovery of known compounds from the
samespecies(KoehnandCarter,2005). Communities: Pyrosequencing and Fosmid
Currently, the discoveries of new natural metabolites are Library
focusing on non-Streptomyces or rare actinobacteria. Rare
actinobacteria are always referred to as strains that are difficult Molecular phylogenetic studies have shown that only a small
to isolate and might correspond to the unmatched source number (∼1%) of bacterial diversity present in environmental
of new natural metabolites (Baltz, 2006). The bioactivity samples,arereadilycultivableusingconventionalculture-based
studies of natural metabolites from the mangrove rare techniques(Yanetal.,2013).Itisevidentthatmorethan88%of
actinobacteria has become popular. Compounds discovered isolatesbelongtofourphylaknownasProteobacteria,Firmicutes,
from the mangrove rare actinobacteria are uniquely structured Actinobacteria, and Bacteroidetes (Nikolaki and Tsiamis, 2013).
and lead directly to the development of novel antibiotics The uncultivated bacteria may serve as a prolific source of
that are effective against antibiotic-resistant pathogens newbioactivecompoundsastheymaypossessagreatdiversity
(Lam,2006). of enzymes to be easily adapted to different environmental
conditions. Unlike other strategies used for novel enzyme and
Mangrove microorganismidentification,themetagenomicmethodhasclear
advantages as an alternative to culture dependent methods.
Mangrove swamps occupy about 181,000km2 (Jusoff, 2013) or Metagenomics is a culture-independent genomic analysis of
coverapproximately75%oftheworld’stropicalandsubtropical bacteria diversity contained in a sample, reducing difficulties
coastlines (Yang et al., 2013). Mangroves are mostly tropical related to conditions for bacteria cultivation (Handelsman,
trees that grow between the high spring tide mark in stable 2004). Metagenomics uses different methods ranging from the
shores,andnearmeansealevels(Holguinetal.,2001).According generation of short sequence reads by direct use of high-
to Tomlinson (1986), a mangrove requires five criteria to be throughput sequencing technologies, to the construction and
considered a “true or strict mangrove” namely, (1) complete sequencingoflarge-insertDNAlibraries(Reigstadetal.,2011).
fidelity to the mangrove environment; (2) plays a major role Nextgenerationsequencing(NGS)hassignificantlyincreased
in the structure of the community and has the ability to form sequencing output via the use of extremely parallel sequencing
pure stands; (3) morphological specialization for adaptation (Staley et al., 2013). The advancement of the next-generation
to the habitat; (4) physiological specialization for adaptation DNA sequencing technologies such as high-throughput
to their habitat; and (5) taxonomic isolation from terrestrial pyrosequencing and Illumina platform, increases scientific
relatives.Mangrovesarethusauniqueenvironmentwithhighly interests in understanding the microbial diversity in different
productive ecosystems (global litterfall of 100 Tg C year−1) environments. The study of bacterial communities from soils
(JennerjahnandIttekkot,2002).Theimportantphysicalfeatures (Jonesetal.,2009),marinewater(Brownetal.,2009),wastewater
of the mangrove that aid their survival in the boundary zone (Sanapareddyetal.,2009)andhumanmicrobiomes(NIHHMP
betweenoceanandlandareadaptationsformechanicalfixation Working Group et al., 2009) have been successfully conducted
in loose soil, specialized dispersal mechanisms, breathing roots using the NGS approach. High-throughput pyrosequencing
andairexchangedevices,andspecializedmechanismsfordealing is a tool for the analysis of environmental microbiome, and
withexcesssaltconcentration(Spaldingetal.,1997). reveal the taxonomic diversity of a specific environment at
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Azmanetal. Mangroverareactinobacteria
high resolution (Zhu et al., 2011). This method enables rapid and Verrucomicrobia. The formation of metagenomic libraries
estimation of bacterial diversity and furthermore, provides using fosmid library become a method of choice for exploring
information about environmental interference. The NGS environmental microbial communities that are difficult to
approachenablesthediscoveryofnovelenzymesandmolecules cultureandmaintain.
with potential application in the biotechnology industry (Duan
and Feng, 2010). The NGS technology is known to be costly Actinobacteria
for the assessment of huge numbers of environmental samples
with high sequencing depths (Zhou et al., 2011). However, Under the domain Bacteria, the Actinobacteria is one of
the advancement in NGS technology has enabled Illumina the most distributed phyla among the 30 major lineage
to dominates the market with 60% of the second generation including 5 subclasses (www.bacterio.net). According to
sequencerinstallationthatsuccessfullyreducingthecostwiththe Zhi et al. (2009), under the class Actinobacteria, there are
usedofreversibleterminator-basedsequencingbythesynthesis five orders known as Acidimicrobiales, Rubrobacterales,
chemistry, small, and less expensive, Illumina MiSeq platform Coriobacterales,Bifidobacteriales,andActinomycetales.However,
(Niedringhausetal.,2011). the recent list showed that there are five new orders under
TheapplicationofNGSallowsthestudyofmicrobialdiversity Actinobacteria known as Nitriliruptorales (Sorokin et al.,
without culturing the bacteria hence, avoiding the loss of 2009), Solirubrobacterales (Reddy and Garcia-Pichel, 2009),
unculturable bacteria on laboratory media such as fastidious Thermoleophilales (Reddy and Garcia-Pichel, 2009), Euzebyales
bacteria. The latest metagenome study on characterization (Kurahashi et al., 2010), and Gaiellales (Albuquerque et al.,
of mangrove soil collected from Rantau Abang, Malaysia 2011), making a total of ten orders (www.bacterio.net). In
via NGS was done by Chan and Ismail (2015). In this nature, Actinobacteria are also known as saprophyte soil
study, they showed that the Proteobacteria (43.72%) was inhabitants (Naik et al., 2013), and one of the dominant
the dominant phyla followed by Acidobacteria (17.68%), colonizers in soils (McCarthy and Williams, 1992; Heuer et al.,
Firmicutes(13.45%),Actinobacteria(4.55%),Nitrospirae(4.22%), 1997;Leeetal.,2012).ActinobacteriaareGrampositivebacteria
Planctomycetes (3.06%), Chloroflexi (2.88%), Verrucomicrobia with a high G+C content in their DNA, ranging from 51% in
(2.69%), Spirochaetes (1.70%), Chlamydiae (1.32%), and some corynebacteria, to more than 70% in Streptomyces and
Bacteroidetes (1.31%). However, the unclassified bacteria found Frankia except for Tropheryma whipplei; an obligate pathogen
in this study were clustered as Caldithrix, Haloplasmatales, whichcontainslessthan50%G+C(Marcoetal.,2007).
and phototrophic bacteria. A study on the profile of bacterial Actinobacteria have a variety of morphologies, from rod-
communityindifferentdepthsofsoilinSundarbansmangrove, coccoid (e.g., Arthrobacter spp.) or coccoid (e.g., Micrococcus
India was done by Basak et al. (2015). The taxanomic analysis spp.), to permanent or highly differentiated branch mycelium
of 2746 species showed that they belong to 33 different phyla (e.g., Streptomyces spp.), or fragmenting hyphal forms
such as Proteobacteria, Firmicutes, Chloroflexi, Bacteroidetes, (e.g., Nocardia spp.) (Atlas, 1997). They also show various
Acidobacteria, Nitrospirae, and Actinobacteria. The description physiological and metabolic properties, such as the production
of mangrove microbiology has been made on the basis of ofextracellularenzymesandavarietyofsecondarymetabolites
pyrosequencing, based on DNA extracted directly from the such as potent antimicrobial agents (Lee et al., 2014a; Olano
sediment of four distinct mangrove areas along the coast etal.,2014).ThememberofgenusStreptomycesspeciesdisplayed
of the Sao Paulo State in Brazil (Andreote et al., 2012). rare development characteristics with the formation of aerial
The major bacterial phyla identified from this study was myceliumwithspore(Leeetal.,2014b;Seretal.,2015),whereas
Proteobacteria (47.1—56.3%) followed by Firmicutes (10.5— certain mycobacterium exhibited a persistent non-replicating
13.8%),Actinobacteria(5.4—12.2%),Bacteroidetes(3.8—11.8%), state.Incommonlaboratorymedia,Actinobacteriatendstogrow
and Chloroflexi (1.3—5.4%); and some minor phyla such as slowly as branching filaments and have the ability to produce
Planctomytes, Cyanobacteria, Acidobacteria, and Archaea. motile spores (Nanjwade et al., 2010). Actinobacteria can be
Furthermore, Andreote et al. (2012) compared the mangrove dividedintotwomaingroups;theStreptomyces,representingthe
metagenomes with other related studies, which indicated that dominantspeciesinthegroup;andtherareactinobacteria.
the phylum Actinobacteria was mostly found in estuarine
sediments.ThemetagenomicdatafromThompsonetal.(2013) Rare Actinobacteria
showed similar predominant bacterial phyla in two different
mangrove areas in Brazil, namely Rio de Janeiro and Bahia; In their natural habitat, Streptomyces are the dominant species
were Proteobacteria (57.8% and 44.6%), Firmicutes (11% and of Actinobacteria. Rare actinobacteria are relatively difficult
12.3%), and Actinobacteria (8.4% and 7.5%). Furthermore, the to isolate, culture, and maintain; due to the difficulties in
Actinobacteria, Fibrobacteres/Acidobacteria, and Firmicutes maintaining and mimicking their natural environment. Rare
group were predominantly represented in the Bahia mangrove actinobacteria have been considered as Actinobacteria with
area. Gomes et al. (2010) performed an educated measurement lower isolation rates compared to Streptomyces strains using
of rhizosphere microbial population in comparison to bulk conventionalisolationmethods,duetotherequirementofusing
sediments samples. The major bacterial order discovered were appropriateisolationproceduresandtoapplydifferentselection
Burkholderiales,Caulobacterales,andRhizobialswhilethemajor conditions (Khanna et al., 2011). Until September 2010, there
bacterial phyla discovered were Acidobacteria, Actinobacteria, are approximately 220 genera of rare actinobacteria reported
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Azmanetal. Mangroverareactinobacteria
(Tiwari and Gupta, 2013). More evidences have shown that on the diversity of actinobacteria from a Malaysian mangrove
increasingnumbersofrareactinobacteriahavebeendiscovered forest showed that 40.2% of isolates were rare actinobacteria
from different sources, thus indicating that rare actinobacteria andthepredominantgenuswasMycobacterium.Thestudyalso
are widely distributed in the biospheres. Even though soils and discoveredothergeneraofrareactinobacteria,suchasLeifsonia,
wateraretheirmajorhabitat,theyarealsoisolatedfromdifferent Streptacidiphilus, Sinomonas, and Terrabacter, which were not
environmentssuchasthedeepocean,desert,mangroves,plants, commonly found in mangrove environment. In this study, the
caves,volcanicrocks,andstones(Grothetal.,1999).Innatural understandingofrareactinobacteriadiversityledtothediscovery
ecosystems, many chemical, biological, and physical elements; of novel genus and species strains, such as “Microbacterium
affect their diversity as the environmental factors such as pH, mangrovi sp. nov.” (Lee et al., 2014c), “Mumia flava gen. nov.,
humuscontent,soilstype,temperature,andsalinityaffecttheir sp. nov.” (Lee et al., 2014d) and Sinomonas humi sp. nov.”
distribution(Hayakawa,2008). (Lee et al., 2015) isolated from a mangrove forest in Tanjung
The isolation of rare actinobacteria could definitely increase Lumpur, Malaysia. The discoveries of novel rare actinobacteria
the chances of discovering potentially novel bioactive frommangroveenvironments,from2001until2015arelistedin
compounds, therefore it is vital to be equipped with better Table1.
knowledgeoftheirdiversityanddistributionintheenvironment;
in order to facilitate the isolation of these strains using an Natural Compounds from Rare
efficient approach (Hong et al., 2009; Tiwari and Gupta, 2012; Actinobacteria
Leeetal.,2014a).AccordingtoJoseandJebakumar(2013),rare
actinobacteria are distributed among 24 genera: Actinomadura, Thediscoveryofthefirstantibiotic,penicillin,in1929heralded
Actinoplanes, Amycolatopsis, Actinokineospora, Acrocarpospora, the era of antibiotics. Streptomycin was later isolated from
Actinosynnema, Catenuloplanes, Cryptosporangium, Streptomyces griseus by Waksman in 1943, while vancomycin
Dactylosporangium, Kibdelosporangium, Kineosporia, wasdiscoveredin1953asametaboliteoftherareactinobacteria
Kutzneria, Microbiospora, Microtetraspora, Nocardia, strain, Amycolatopsis orientalis (Mahajan and Balachandran,
Nonomuraea, Planomonospora, Planobispora, Pseudonocardia, 2012). The discovery of various useful antibiotics from rare
Saccharomonospora, Saccharopolyspora, Saccharothrix, actinobacteriacontributesasanimportantpartinthediscovery
Streptosporangium,andSpirilliplanes. of novel natural products (Ara et al., 2013). Researchers
understand the role of microorganisms to provide rich sources
RareActinobacteriaofMangroveOrigin ofusefulnaturalproductsforclinicalpurposes(Subramaniand
The mangrove ecosystem is among the world’s most Aalbersberg, 2012). The demand for new drugs in the world is
productive environment, and it is a huge unexplored source of extremelyurgentandextensiveduetothefastspreadofdiseases,
Actinobacteriawithahighpotentialtoproduceactivesecondary common ailments, and the fast spread of antibiotic-resistant
metabolites(Hongetal.,2009).Indeedrelativelylittleisknown pathogens (Jiang et al., 2008). The continuous advancement in
abouttherareactinobacterialivinginthemangroveecosystem. scienceandtechnologywouldenabletheaccelerateddiscoveryof
Recentlythemangroveecosystemhasbecomepopularfornovel usefulbioactivecompoundsfromprolificproducerssuchasthe
strainsandnovelbioactivecompounddiscovery. Actinobacteria.
A few reports from different geographical locations globally As of the year 2002, over 10,000 bioactive compounds (45%
have described the diversity and isolation of novel rare of all microbial metabolites) were produced by filamentous
actinobacteriaindifferentmangrovehabitats.In2008,Eccleston Actinobacteria, out of which 7600 (75%) were derived from
et al. reported the occurrence of Microsmonospora from the Streptomyces, and 2500 (25%) from rare actinobacteria such as
Sunshine Coast in Australia (Eccleston et al., 2008). Xie Micromonospora,Actinomadura,andStreptoverticillium(Bérdy,
et al. (2006) and Huang et al. (2008) reported the isolation 2005). Actinobacteria are able to produce different types of
of a rifamycin-producing Micromonospora from mangrove in secondary metabolites due to the function of various genes
South China Sea. Different genera such as Brevibacterium, such as the non-ribosomal polyketides synthase (NRPS) and
Dermabacter, Kytococcus, Microbacterium, Nesterenkonia, and polyketidesynthase(PKS)(Salomonetal.,2004;Leeetal.,2014a).
Rothia were isolated from mangrove sediments in Brazil (Dias In spite of the tremendous success of the past in screening
et al., 2009b). In China, a number of rare actinobacteria for useful secondary metabolites, the chance of finding new
including Actinomadura, Isoptericola, Microbispora, Nocardia, biologically active molecules from Streptomyces has decreased
Nonomuraea, and Rhodococcus; were isolated from mangrove (Fenicaletal.,1999).AssomeStreptomycesstrainsfromdifferent
soils and plants (Hong et al., 2009). Results from Ara et al. environmentsproducedthesametypesofcompounds,possibly
(2013) showed that 17 different genera of rare actinobacteria duetofrequentgeneticexchangebetweenspecies(Bredholtetal.,
were identified from a total of 241 isolates. It is reported 2008;Freeletal.,2011).Asaresult,thereisadramaticincreasein
that the predominant genus detected was Micromonospora in demandtolookfornewpharmacologicalimportantcompounds.
bothmangroveandmedicinalplantrhizospheresoilsamplesin The advancement of new selective techniques enables the
Dhaka, Bangladesh. This result was in line with other studies isolation and screening of rare actinobacteria, which could
(Cross,1981;JiangandXu,1996;Hatano,1997;Araetal.,2002) lead to the discovery of new and useful bioactive compounds.
which exhibited Micromonospora was the predominant genus The discovery of rare actinobacteria has enlarged the range
in isolates from wet soil. A study done by Lee et al. (2014a) and diversity of genetic resources available for biotechnological
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Azmanetal. Mangroverareactinobacteria
TABLE1|Novelmangroverareactinobacteriadiscoveredbetweentheyears2001and2015.
Genus Strainnameanddesignation Sources References
Agromyces Agromycesluteolus,8T,Agromyces RhizosphereofmangrovesintheestuaryoftheShiiraRiver, TakeuchiandHatano,2001
rhizospherae,14T,Agromycesbrachium,65T IriomoteIsland,Japan
Asanoa Asanoairiomotensis,TT97-02T SoilatrootsofthemangroveBruguieragymnorrhiza TamuraandSakane,2005
Polymorphospora Polymorphosporarubra,TT97-42T SoilneartherootsofBruguieragymnorrhizaandSonneratiaalba Tamuraetal.,2006
attheRiverShiira,IriomoteIsland,Okinawa,Japan
Nonomuraea NonomuraeaMaheshkhaliensis,16-5-14T MangroveforestinMaheshkhali,Cox’sBazar,Bangladesh Araetal.,2007
Micromospora Micromonosporapattaloongensis,TJ2-2T MangroveforestinPattaloongProvince,Thailand Thawaietal.,2008
Micromonospora Micromonosporarifamycinica,AM105T MangrovesedimentcollectedfromtheSouthChinaSea Huangetal.,2008
Actinomadura Actinomaduramaheshkhaliensis,13-12(50)T MangroverizhospheresoilsofMaheshkhali,Bangladesh Araetal.,2008
Verrucosispora Verrucosisporalutea,YIM013T ShenzhenFutianMangrove Liaoetal.,2009
Demequina Demequinasalsinemoris,KV-810T MangrovesoilfromasouthernislandinJapan Matsumotoetal.,2009
Sphaerisporangium Sphaerisporangiumkrabiense,A-T0308T TropicalmangroveforestsoilfromThailand Suriyachadkunetal.,2011
Isoptericola Isoptericolachiayiensis,06182M-1T MangrovesoilfromChiayiCountryinTaiwan Tsengetal.,2011
Micromonospora Micromonosporarhizosphaerae,211018T MangroveExcocariaagallocharhizospheresoil Wangetal.,2011a
Nonomuraea Nonomuraeawenchangensis,210417T Mangroverhizospheresoil Wangetal.,2011b
Jishengella Jishengellaendophytica,202201T Acanthusillicifoliusrootfromthemangrovereservezonein Xieetal.,2011
Hainan,China
Asanoa Asanoahainanensis,210121T RhizospheresoilofthemangrovefernAcrostichumspeciosum Xuetal.,2011
Microbispora Microbisporahainanensis,211020T RhizospheremangrovesoilofExoecariaagallocha,Hainan,China Xuetal.,2012
Lysinimicrobium Lysinimicrobiummangrovi,HI08-69T RhizospheremangrovesoilsfromIriomoteIsland,Japan Hamadaetal.,2012
Verrucosispora Verrucosisporaqiuiae,RtIII47T MangroveswampinSanya,HainanProvince,China Xietal.,2012
Actinomadura Actinomadurasediminis,YIMM10931T MangrovesedimentsfromDugongCreel,LittleAndaman,India Heetal.,2012
Agromyces Agromycesindicus,NIO-1018T MangrovesedimentoftheChoraoIsland,Goa,India Dastageretal.,2012
Micromonospora Micromonosporahaikouensis,232617T CompositemangrovesedimentfromHaikou,China Xieetal.,2012
Micromonospora Micromonosporamaritime,D10-9-5T MangrovesoilinSamutSakhonprovince,Thailand Songsumanusetal.,2013
Micromonospora Micromonosporaavicenniae,268506T RootofAvicenniamarinacollectedatmangroveforestin Lietal.,2013a
Wengchang,Hainanprovince,China
Actinoallomurus Actinoallomurusacanthiterrae,2614A723T RhizospheresoilofmangroveplantAcanthusilicifoliusfrom Tangetal.,2013
Touyuan,Wenchang,Hainanprovince,China
Micromonospora Micromonosporasonneratiae,274745T RootofSonneratiaapetalafrommangroveforestinSanya,Hainan Lietal.,2013b
province,China
Micromonospora Micromonosporawenchangensis, CompositemangrovesoilfromWenchang,Hainanprovince,China Renetal.,2013
2602GPT1-05T
Microbacterium Microbacteriummangrovi,MUSC115T MangrovesoilofTanjungLumpurriver,StateofPahang,Malaysia Leeetal.,2014c
Mumia Mumiaflava,MUSC201T MangrovesoilofTanjungLumpurriver,StateofPahang,Malaysia Leeetal.,2014d
Sinomonas Sinomonashumi,MUSC117T MangrovesoilofTanjungLumpurriver,StateofPahang,Malaysia Leeetal.,2015
exploitation. It is apparent that the discovery of novel rare organotrophic (Ann and Maria, 2009). Currently, this genus
actinobacteria can be expected to provide new bioactive contains59speciesand7subspecies(http://www.bacterio.net/).
compounds (Lazzarini et al., 2000; Donadio et al., 2002; Redenbach et al. (2000) revealed that Micromonospora chalcea
TakahashiandÔmura,2003;Bérdy,2005;Hongetal.,2009;Lee DSM 43026 contained a linear chromosome with a size of 7.7
etal.,2014a). Mb.Hirschetal.(2013)reportedthecompletegenomesequence
The review mainly focuses on five different genera with ofMicromonosporastrainL5isolatedfromnodulesofCasuarina
the species found from the mangrove environment namely, equisetifolia trees in Mexico. The strain Micromonospora strain
Micromonospora,Jishengella,Salinispora,Saccharopolyspora,and L5hasagenomesizeof6,907,073bp,with6332predictedopen
Nocardiopsis. They are all proven to have valuable sources of reading frames (ORFs) and the GC content of 72.86%. The
potentialmetabolitesandbesidesStreptomyces;theyhaveproven genomewassequencedusingacombinationofIlluminaand454
tobevaluablesourcesofpotentiallyusefulbioactivemetabolites. technologies at the Joint Genome Institute (JGI). According to
Hirsch and Valdés (2009), the genome size of Micromonospora
Micromonospora aurantica is 6.97 Mb and contains 88.64% of GC. However,
Micromonospora is a genus of Actinobacteria from the both genomes of Micromonospora aurantianca ATCC 37029
Micromonosporaceae family. This genus was first isolated and Micromonospora strain L5 have not been annotated
by Ørskov in 1923, is Gram positive, aerobic, and chemo- asyet.
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Azmanetal. Mangroverareactinobacteria
Currently, some Micromonospora from the mangrove (the (3-hydroxyl) derivative of ikarugamycin) and protonated
environment has produced useful bioactive compounds for aromatic tautomer of 5′-methylthioinosine (MTI) (4). The
studiesondrugdiscovery.MicromonosporarifamycinicaAM105 antibacterial activity for butremycin showed it was not potent
was isolated from mangrove sediments from Hainan Island, enough to kill pathogens such as Staphylococcus aureus ATCC
SouthChinaSea(Huangetal.,2009).Theantimicrobialactivity 25923, Escherichia coli ATCC 25922, and clinical isolates of
againstmethicillin-resistantStaphylococcusaereus(MRSA)using methicillin-resistantStaphylococcusaureus(MRSA)strains.The
′
secondary metabolite extracts has led to the discovery of two antimicrobialactivityoftheprotonatedaromatictautomerof5-
antibiotic compounds (Figure1), namely rifamycin S (1) and methylthioinosineshowednoantibacterialactivityagainstthese
the geometric isomer of rifamycin S (2). There are different pathogens.
types of rifamycin, depending on its chemical structure such Micromonospora sp. M2DG17 was isolated from composite
as rifamycin B, O, S, and SV. Rifamycin S has higher activity mangrove sediment in Haikou, China (Huang et al., 2011).
once it reduces to form rifamycin SV in aqueous solutions The utilization of bioassay-guided fractionation enabled
(Zhang,2003).Alsotheantibacterialactivityfromacombination 5 compounds to be identified for the first time from the
of rifamycin S and the geometric isomer of rifamycin S from Micromonospora species along with two other compounds
MicromonosporarifamycinicaAM105washigherthanrifamycin (Figure3). The five compounds were identified as 3-
SV. This finding suggests that the antibacterial activity of the hydroxymethyl-β-carboline (5), 3-methyl-β-carboline (6),
geometric isomer of rifamycin S was higher than rifamycin SV, β-carboline (7), Cyclo-(L-Pro-L-Phe) (8), and Cyclo-(L-
and the antimicrobial activity of rifamycin SV was higher than Pro-L-Leu) (9) and the other two known compounds were
rifamycinS. Cyclo-(L-Pro-L-Ile) (10) and Cyclo-(L-Pro-L-Val) (11). An
Kyeremeh et al. (2014) discovered an actinobacterial strain, antitumor study using 3-methyl-β-carboline resulted in weak
Micromonospora sp. K310, from Ghanaian mangrove river inhibitory on human colon carcinoma; HCT 116 cell lines
sediment. The spectroscopy study of this strain led to the (Huangetal.,2011).
discovery of two new compounds (Figure2), butremycin (3)
Jishengella
Anovelgenus,Jishengella,proposedbyXieetal.(2011);isone
oftherareactinobacteriawithintheMicromonosporaceaefamily.
JishengellaisthegenusnamegivenbyaChinesemicrobiologist,
Jisheng Ruan. Currently, the genus consists of one species
identifiedasJishengellaendophytica202201T(Xieetal.,2011).
Strain Jishengella endophytica 161111 has been able to
produce a new alkaloid identified as 2-(furan-2-yl)-6-(2S,3S,4-
trihydroxybutyl) pyrazine (12) (Wang et al., 2014). Extraction
from the Jishengella endophytica 161111 fermentation broth
resultedintheidentificationofthreepyrazinederivatives(12,13,
14),fourpyrrololactones(15,16,17,18),threeβ-carbolines(19,
20, 21), 1H-indole-3-carboxaldehyde (22), 2-hydroxy-1-(1H-
indol-3-yl) ethanone (23), and 5-(methoxymethyl)-1H-pyrrole-
FIGURE1|ThestructureofrifamycinS(1)andthegeometricisomer
2-carbaldehyde (24) (Wang et al., 2014). All compounds found
ofrifamycinS(2).
inJishengellaendophytica161111areshowninTable2.
FIGURE2|Thestructureofbutremycin(3)andprotonatedaromatictautomerof5′-methylthioinosine(MTI)(4).
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Azmanetal. Mangroverareactinobacteria
FIGURE3|Thestructureof3-hydroxymethyl-β-carboline(5),3-methyl-β-carboline(6),β-carboline(7),Cyclo-(L-Pro-L-Phe)(8),and
Cyclo-(L-Pro-L-Leu)(9),Cyclo-(L-Pro-L-Ile)(10),andCyclo-(L-Pro-L-Val)(11).
AllcompoundsextractedfromJishengellaendophytica161111 demonstratedweakcytotoxicactivityagainstMadin-Dadycanine
were tested for antivirus effects on influenza A (H1N1) virus kidney(MDCK)normalcells.
usingthecytopathiceffect(CPE)inhibitionassayadaptedfrom The β-carboline alkaloids are one of the largest groups of
Grassauer et al. (2008) and Hung et al. (2009). Results showed natural and synthetic indole alkaloids that have a common
that compounds 14, 20, 21, and 22 displayed moderate anti- tricyclic pyrido [3,4-b] indole ring structure (Allen and
H1N1activity(Wangetal.,2014).Furthermore,allcompounds Holmstedt,1980).Originally,thiscompoundwasisolatedfrom
weretestedforcytotoxiceffectsasdescribedinMosmann(1983). the plant, Peganum harmala (Zygophillaceae) located in the
The study showed that only compounds 14, 20, 21, and 22; Middle East, India, and North Africa. It was used as an
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Azmanetal. Mangroverareactinobacteria
TABLE2|NaturalcompoundsdiscoveredfromJishengellaendophytica161111.
Compounds References
PYRAZINEDERIVATIVES
2-(furan-2-yl)-6-(2S,3S,4-trihydroxybutyl)pyrazine(12) Wuetal.,2007
2-(furan-2-yl)-5-(2S,3S,4-trihydroxybutyl)pyrazine(13) Wuetal.,2007
Lumichrome(14) Dingetal.,2009
PYRROLOLACTONES
(S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(15) Sannaietal.,1982
(S)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(16)
Sannaietal.,1982
(4S)-4-(2-methylbutyl)-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(17) Sannaietal.,1982;Tressletal.,1995
(S)-4-benzyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(18) Jericetal.,2000
(Continued)
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Azmanetal. Mangroverareactinobacteria
TABLE2|Continued
Compounds References
β-CARBOLIN
Flazin(19) Suetal.,2002
Perlolyrine(20) Dassonnevilleetal.,2011
1-hydroxy-β-carboline(21) Jiaoetal.,2010
1H-indole-3-carboxaldehyde(22) YangandCordell,1997;Ashouretal.,2007
2-hydroxy-1-(1H-indol-3-yl)ethanone(23) YangandCordell,1997;Ashouretal.,2007
5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde(24) Donetal.,2005
effective traditional herbal drug for its abortifacient effect, and Salinispora
emmanagogs (Moloudizargari et al., 2013). A study done by SalinisporaisagenuswithinthefamilyMicromonosporaceaethat
Wang et al. (2014) showed that the simple β-carboline isolated was isolated from marine sediment in 2005 (Maldonado et al.,
from Jishengella endophytica 161111 was able to kill the H1N1 2005).SalinisporaisanaerobicandGrampositivebacteriumthat
virus.TheunsubstituedH-3isimportantinanti-H1N1activity formedextensivebranchedsubstratehyphaewith0.25–0.5µmin
ofthiskindofcompounds. diameter.ItisthefirstActinobacteriathatrequiresseawaterto
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Azmanetal. Mangroverareactinobacteria
grow(Maldonadoetal.,2005).Currently,thegenusSalinispora Saccharopolyspora
consistsofthreespecies,namelySalinisporaarenicola,Salinispora The genus Saccharopolyspora was discovered in 1974 by Lacey
tropica,(Maldonadoetal.,2005),andSalinisporapacifica(Jensen and Goodfellow from heated sugar cane bagasse (Guan et al.,
andMafnas,2006). 2011). At the time of writing, the genus Saccharopolyspora
Udwary et al. (2007) reported the first complete genome contained 26 species and 3 subspecies isolated from various
of rare actinobacteria, Salinispora tropica CNB-440. This strain sources (http://www.bacterio.net/). The first complete genome
consists of 5,183,331 bp in size, which is approximately 3 Mbp sequenceoftheSaccharopolysporastrainwasreportedbyOliynyk
smallerthanthegenomeofStreptomyces(BullandStach,2007). et al. (2007). The genome size of Saccharopolyspora erythraea
Analysisonthesecondarynaturalproductgeneclustersshowed is about 8.3 Mbp predicted to encode 7264 genes. S. erythraea
that Salinispora tropica contains approximately 9.9% of the genomecontainsatleast25geneclustersfortheproductionof
genomes dedicated to secondary metabolism, which is greater known or predicted secondary metabolites. The draft genome
than previous Streptomyces coelicolor (≈8%) as well as other ofSaccharopolyspora spinosaNRRL18395wasreportedbyPan
naturally-producing Actinobacteria (Udwary et al., 2007). The etal.(2011)whichconsistsofapproximately8.6MbpwithaGC
genome sequence of Salinispora revealed a great number of contentof67.94%.ThelatestdraftgenomeofSaccharopolyspora
novelbiosyntheticgeneclusters,andbasedontheanalysis;these rectivirgula was reported by Pettersson et al. (2014). The draft
findingsconfirmsthatthisgenusisoneoftheimportantsources genome of this strain consists of 182 contigs totaling 3,977,051
ofnoveldrug-likemolecules.AccordingtoBullandStach(2007), bpwithaGCcontentof68.9%.
15 secondary metabolite gene clusters have been identified in Izumikawa et al. (2012) isolated Saccharopolyspora sp. RL78
Salinisporatropica. from mangrove soil in Nosoko, Ishigaki Island, Okinawa
A significant feature of Salinispora tropica is its ability to Prefecture, Japan. They discovered a new cyclizidine analog
producestructurallyuniquesecondarymetabolites.Felingetal. named JBIR-102 (26) (Figure5), which exhibited cytotoxic
(2003) reported that the Salinispora tropica CNB-392 isolated activity against HeLa cells and human malignant pleural
fromamangroveareainChubCay,Bahamasproducedaunique mesotheliomacellline,ACC-MESO-1.
metabolite named salinosporamide A (25) (Figure4) attached
with γ-lactam-β-lactone bicyclic core with clasto-lactacystin-β- Nocardiopsis
lactone(alsocalledasomuralide),ametabolitediscoveredfrom NocardiopsisisagenusofthefamilyNocardiopsaceaediscovered
terrestrialStreptomycessp.Thestudyshowedthatthiscompound in1976byMeyer.Thebacteriumcontainsfragmentingmycelium
was able to kill different degrees of cancer cells and possessed and a cell wall containing meso-diaminopimelic acid with no
strong inhibition of the 20S proteasome. Salinosporamide A diagnostically important carbohydrates (Li et al., 2012). The
was tested for the effects on proteasome function due to genus Nocardiopsis contains 45 species and 5 subspecies with
its structural relationship to omuralide. Results exhibited that validly published names (http://www.bacterio.net/). The first
Salinosporamide A was 35 times more potent compared to reportongenomesequenceofgenusNocardiopsiswasreported
omuralide.Currently,theSalinosporamideAisinphaseIhuman by Sun et al. (2010). Members of Nocardiopsis dassonvillei
clinical trials as a potential anticancer drug (Fenical et al., have been isolated from a variety of natural habitats such as
2009). soilsandmarinesediments,plant,animalmaterial,andhuman
patients. According to Sun et al. (2010), the genome size of
Nocardiopsisdassonvilleiis6,543,312bpwitha73%GCcontent,
and3.3%ofgeneclusterisforsecondarymetabolitebiosynthesis,
FIGURE4|ThestructureofSalinosporamideA(25). FIGURE5|ThestructureofJBIR-102(26).
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