rare actinobacteria from medicinal plants of tropic al rainforests

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1 Rare actinobacteria from medicinal plants of tropical rainforests, 1 Xishuangbanna: isolation, diversity and antimicrobial activity 2 Sheng Qin 1 , Jie Li 1 , Hua-Hong Chen 1, 2 , Guo-Zhen Zhao 1 , Wen-Yong Zhu 1 , 3 Cheng-Lin Jiang 1 , Li-Hua Xu 1 , Wen-Jun Li 1* 4 1. The Key Laboratory for Microbial Resources of the Ministry of Education, P. R. 5 China, and Laboratory for Conservation and Utilization of Bio-Resources, Yunnan 6 Institute of Microbiology, Yunnan University, Kunming, 650091, P. R. China 7 2. Department of Chemistry, Chuxiong Normal College, Chuxiong, Yunnan, 675000, P. 8 R. China 9 10 * Author for correspondence: Wen-Jun Li 11 Tel & Fax: +86 871 5033335 12 E-Mail: [email protected] ; [email protected] 13 14 15 Running title: Rare actinobacteria from medicinal plants of tropical rainforests 16 17 18 19 20 21 22 Copyright © 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved. Appl. Environ. Microbiol. doi:10.1128/AEM.01034-09 AEM Accepts, published online ahead of print on 31 July 2009 on April 11, 2019 by guest http://aem.asm.org/ Downloaded from

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Page 1: Rare actinobacteria from medicinal plants of tropic al rainforests

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Rare actinobacteria from medicinal plants of tropical rainforests, 1

Xishuangbanna: isolation, diversity and antimicrobial activity 2

Sheng Qin1, Jie Li

1, Hua-Hong Chen

1, 2, Guo-Zhen Zhao

1, Wen-Yong Zhu

1, 3

Cheng-Lin Jiang 1

, Li-Hua Xu1, Wen-Jun Li

1* 4

1. The Key Laboratory for Microbial Resources of the Ministry of Education, P. R. 5

China, and Laboratory for Conservation and Utilization of Bio-Resources, Yunnan 6

Institute of Microbiology, Yunnan University, Kunming, 650091, P. R. China 7

2. Department of Chemistry, Chuxiong Normal College, Chuxiong, Yunnan, 675000, P. 8

R. China 9

10

*Author for correspondence: Wen-Jun Li 11

Tel & Fax: +86 871 5033335 12

E-Mail: [email protected] ; [email protected] 13

14

15

Running title: Rare actinobacteria from medicinal plants of tropical rainforests 16

17

18

19

20

21

22

Copyright © 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.Appl. Environ. Microbiol. doi:10.1128/AEM.01034-09 AEM Accepts, published online ahead of print on 31 July 2009

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Abstract 23

Endophytic actinobacteria are relatively unexplored as potential sources of novel 24

species and novel natural products for medical and commercial exploitation. 25

Xishuangbanna is well recognized in the world for its diverse flora, especially the 26

rainforest plants, many of which have indigenous pharmaceutical history. However, 27

little is known about the endophytic actinobacteria from this tropical area. In this 28

work, we studied the diversity of actinobacteria isolated from medicinal plants 29

collected from tropical rainforests in Xishuangbanna. Due to the use of different 30

selective isolation media and methods, a total of 2174 actinobacteria were isolated. 46 31

isolates were selected on the basis of their morphology on different media and were 32

further characterized by 16S rRNA gene sequencing. The results showed that they 33

represent an unexpected variety of 32 different genera. To our knowledge, this is the 34

first report describing isolation of Saccharopolyspora, Dietzia, Blastococcus, 35

Dactylosporangium, Promicromonospora, Oerskovia, Actinocorallia and Jiangella 36

species from the endophytic environments. At least 19 isolates are considered as novel 37

taxa by our current research. In addition, all of the 46 isolates were tested for 38

antimicrobial activity and screened for the presence of genes encoding polyketide 39

synthetases (PKS) and nonribosomal peptide synthetases (NRPS). These results 40

confirm that medicinal plants from Xishuangbanna represent an extremely rich 41

reservoir for the isolation of significant diversity of actinobacteria and novel species 42

which are potential sources for discovery of biologically active compounds. 43

44

Keywords: Actinobacteria, Endophytic, Tropical rainforests, Medicinal plants, 45

Diversity 46

47

48

49

50

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Introduction 51

The class Actinobacteria present a high proportion of soil microbial biomass and 52

contain the most economically significant prokaryotes, producing over half of the 53

bioactive compounds in the Antibiotic Literature Database (47), notably antibiotics 54

(7), immunosuppressive agents (57), antitumor agents (20), and enzymes (65), 55

especially those belonging to the genus Streptomyces, which are the excellent 56

producers. The advent of drug resistance in many bacterial pathogens and the current 57

increase in the number of fungal infections has caused a resurgence of interest in 58

finding other reserves of biologically active compounds (64). As the search for novel 59

natural products continues, it becomes apparent that the rate of discovery of new 60

compounds from soil streptomycetes has decreased, whereas the rate of re-isolation of 61

known compounds has increased (29). Recent evidence is being accumulated that rare 62

actinomycete species, which are often very difficult to isolate and cultivate, might 63

represent a unique source of novel biologically active compounds (5). On the other 64

hand, new microbial habitats need to be examined, in the search for novel bioactive 65

compounds. One biologically important but relatively overlooked niche is the inner 66

tissues of higher plants. Early studies have demonstrated that some actinobacteria can 67

form intimate associations with plants and colonize their inner tissues. Frankia 68

species and Streptomyces scabies can penetrate their host and establish either 69

pathogenic or endophytic associations (6, 25). The actinomycete bacteria that reside 70

in the tissue of living plants and do not visibly harm the plants are known as 71

endophytic actinobacteria (37). These actinobacteria are relatively unstudied and are 72

potential sources of novel natural products for exploitation in medicine, agriculture, 73

and industry (74). 74

Endophytic actinobacteria have attracted attention in recent years, with increasing 75

reports of isolates from a range of plant types, including crop plants, cereals, such as 76

wheat, rice, potato, carrots, tomato and citrus (3, 18, 63, 72, 75, 81) and medicinal 77

plants (76, 89) The culturable endophytic actinobacteria from these plants were found 78

to fall within a narrow species distribution, with Streptomyces spp. as the most 79

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predominant species and Microbispora, Micromonospora, Nocardioides, Nocardia 80

and Streptosporangium as the common genera. Endophytic actinobacteria have been 81

demonstrated to improve and promote growth of host plants as well as to reduce 82

disease symptoms caused by plant pathogens through various mechanisms, including 83

the production of secondary metabolites, which are used in direct antagonism against 84

pests and diseases (10, 11, 13), changes in host physiology (42) and induction of 85

systemic acquired resistance in plants (17). Another significant function of these 86

actinobacteria was found to exhibit antibiotic activity, suggesting that endophytic 87

actinobacteria can be an interesting source for bioprospecting. New antibiotics 88

Alnumycin, Munumbacin A-D and Coronamycin have been reported from endophytic 89

Streptomyces spp. (8, 12). Recently, two novel antitumor anthraquinones, lupinacidins 90

A and B were isolated from a new endophytic Micromonospora sp. (43). Moreover, 91

new species of endophytic actinobacteria have been increasingly reported (26, 35). 92

Thus, endophytic actinobacteria are expected to be potential sources of new species 93

and new bioactive agents. 94

Of the myriad of ecosystems on earth, those having the greatest general 95

biodiversity of life seem to be the ones also having the greatest number and most 96

diverse endophytes (74). Tropical and temperate rainforests are the most biologically 97

diverse terrestrial ecosystems on earth that hold the greatest possible resource for 98

acquiring novel microorganisms and their products (74). One of the areas of 99

enormous plant biodiversity is Xishuangbanna, located in P. R. China at the boarder 100

to Myanmar, at the ecotone between the Asian tropics and subtropics, and is 101

dominated by tropical seasonal rain forests (88). It contains over 5000 species of 102

vascular plants, comprising 16 percent of China’s total plant diversity, with more than 103

3000 being endemic species (54, 61), many of which have ethnobotanical history. 104

Until this time, only few researches were carried out on the isolation of endophytic 105

actinobacteria and their secondary metabolites from Xishuangbanna (36, 87). As our 106

long term study on endophytic actinobacterial diversity and bioactive metabolites 107

from tropical rainforest medicinal plants in Xishuangbanna, many bioactive 108

endophytic Streptomyces have been isolated (50). However, this is insufficient to 109

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provide a general understanding of tropical rainforest endophytic actinobacteria 110

regarding to their diversity, distribution, and ecology, as well as for further 111

exploitation of diverse functions of this novel microbial source. 112

In the present study, the diversity of rare endophytic actinobacteria associated 113

with medicinal plants from tropical rainforest in Xishuangbanna was investigated by 114

combined special culturing techniques. The selected isolates were also identified by 115

16S rRNA gene analysis. The overall aims of this study were (i) to analyze 116

actinobacterial community and reveal whether the investigated rainforest in 117

Xishuangbanna represents a valuable source for abundant endophytic actinobacteria 118

and new species, (ii) to evaluate their antimicrobial activities and biosynthetic 119

potential of related secondary metabolites, and (iii) to study the relationships between 120

taxa of these endophytic actinobacteria and applied isolation methods. 121

122

Materials and methods 123

Sample collection 124

An extensive collection of various plant materials was set up in the tropical 125

seasonal rainforest in Xishuangbanna for two years (from November 2005 to May 126

2006 and from September 2006 to June 2007) in the Menglun Nature Reserve 127

(21◦56’N, 101

◦11’S) and Jinghong Nature Reserve (22

◦01’-22

◦19’N, 100

◦47’ 128

-100◦57’S ). Each plant selected for endophyte isolation was based on its local 129

ethnobotanical properties including its properties to antibacterial, insecticidal, 130

antitumour, heal wounds and others. No history indicates that the plants had ever been 131

previously studied for endophytic actinobacteria. Healthy root, stem and leaf samples 132

of each plant were placed in sterile plastic bags and taken to the laboratory, which 133

were subjected to isolation within 96 h. Some representative plants samples of the 134

nearly 90 selected for study are as follows: Phyllanthus urinaria, Kadsura heteroclite, 135

Maesa indica, Rauvolfia verticillata, Paris yunnanensis, Maytenus austroyunnanensis, 136

Gloriosa superba, Scoparia dulcis, Tadehagi triquetrum, Goniothalamus sp., 137

Cephalotaxus sp., and Azadirachta sp. 138

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139

Selective isolation producers and media 140

Samples were air dried for 48 h at room temperature and then washed with an 141

ultrasonic step (160W, 15mim) to remove the surface soils and adhered epiphytes 142

thoroughly. After drying, the samples were subjected to a five-step surface 143

sterilization procedure: a 4 to 10-min wash in 5% NaOCl, followed by a 10-min wash 144

in 2.5% Na2S2O3, a 5-min wash in 75% ethanol, then wash in sterile water, and a final 145

rinse in 10% NaHCO3 for 10-min. After thoroughly drying in sterile conditions, the 146

surface-sterilized tissues were continuously subjected to drying at 100 ºC for 15 147

minutes. Surface treated tissues were then pretreated by a variety of methods 148

described below. 149

Method 1. Most of the samples were aseptically crumbled into small fragments and 150

directly placed on the selective media and incubated at 28 ºC for 2-8 weeks. 151

Method 2. Some samples (1.0 g) treated as above were mixed in a mortar with 0.5 g 152

of sterile powdered calcium carbonate and placed in a Petri dish. 2 ml of sterilized tap 153

water was added to the samples to give a moisture environment. The Petri dish was 154

maintained at 28 ºC for 2 weeks and then air-dried at room temperature to a constant 155

weight. Parts of the samples were directly diluted to 10-4

with sterile water and 156

spread-plated onto media. The other mixtured samples were continuously enriched 157

according to Otoguro et al. (66). Samples were placed in a glass vessel and flooded 158

with 50 ml of 10 mmol-1

phosphate buffer (pH 7.0) containing 10% plant extract or 159

soil extract at 28 ºC for 5 h to liberate actinomycete spores. A portion (10 ml) of the 160

flooding mixture was transferred into a centrifuge tube and centrifuged at 1500×g for 161

30 min. After settling for 30 min, a portion of the supernatant enriched with spores 162

was serially diluted with sterile tap water and plated onto media. 163

Method 3. Some plants, e.g. Maytenus austroyunnanensis, were aseptically 164

crumbled into small fragments and isolated using the combined enzymatic hydrolysis 165

and differential centrifugation method (44). The homogenate was centrifuged at 200 g 166

for 20 min at 4 ºC, and the supernatant was subsequently centrifuged at 3000 g for 30 167

min(4 ºC) to collect the sediments, which will be diluted to 10-2

with sterile water and 168

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spread-plated onto media. 169

200 µl each of the samples pretreated dilutions was spread over the surface of solid 170

media that were designed for cultivation of actinobacteria (Table 1). The inoculated 171

plates were incubated at 28 ºC for 2–4 weeks. The pH of all media was adjusted to 172

7.0-7.4. All media were amended with nalidixic acid (50 mg l-1

) and nystatin (100 mg 173

l-1

) to supress the Gram-negative bacterial and fungal gowth. As the colonies appeared 174

from the plates, they were observed and selected carefully according to their 175

characteristics. Special attention was given to the non-mycelium forming 176

actinobacteria. They were inoculated onto yeast extract-malt extract agar (ISP 2) 177

slants and incubated at 28 ºC for 2–3 weeks. 178

179

Effectiveness of surface sterilization 180

Two experiments were carried out to check the validation of the sterilization 181

procedures. Firstly, the surface-sterilized tissue was imprinted onto the ISP 2 agar, 182

incubated at 28 ºC, then check for microbial growth. Secondly, the surface sterilized 183

samples were washed in sterile distilled water thrice and then soaked in 5ml sterile 184

water and stirred for 1min. An aliquot of 0.2ml suspension was then inoculated on to 185

ISP 2 agar plates, incubated at 28 ºC, and observed for microbial growth. If no 186

microbial growth occurs on the media surface, the sterilization is considered 187

complete. 188

189

Preliminary identification of actinobacteria 190

Isolates were tentatively grouped and dereplicated by observing the morphological 191

and cultural characteristics, including the characteristics of colonies on the plates and 192

slants, the presence of aerial mycelium and substrate mycelium, spora mass colour, 193

distinctive reverse colony colour, diffusible pigment, and sporophore and spore chain 194

morphology. Many colonies that were similar in colour, shape and size, were 195

observed for hyphal length and structure with light microscopes, which allowed them 196

to be segregated into distinct isolates. Cell wall type was also determined on the base 197

of the occurrence of isomers of diaminopimelic acid to exclude the Streptomycetes 198

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from other spore-forming actinomycetes as whole-organism hydrolysates of 199

Streptomyces strains contain the LL-isomer and the latter the meso- diaminopimelic 200

acid. The diagnostic sugars of the representatives of each group were also detected 201

(38). Based on the preliminary grouping, 46 isolates were selected for further 202

research. 203

204

DNA extraction, sequencing and analysis 205

The 46 selected isolates were subjected to 16S rRNA gene sequence analysis for 206

precise genera and species identification. The identity of the organisms was 207

determined based on partial or nearly full length of 16S rRNA gene sequence analysis. 208

Genomic DNA of each isolate was extracted using a method of Li et al. (53). The 16S 209

rRNA genes from pure cultures were amplified using the primer pair PA and PB 210

(Table 2). Polymerase chain reaction was carried out under the following conditions: 211

initial denaturation at 94°C for 4 min, followed by 30 cycles of 94°C for 1 min, 55°C 212

for 1 min and 72°C for 2 min, with a final extension 72°C for 10 min. The reaction 213

mixture (50 µl) contained dNTPs (0.25 mM each), 1×reaction buffer (20 mM Tris pH 214

8.4, KCl 50 mM), MgCl2 (3 mM), primers (1 µM each), Taq DNA polymerase (1.25 215

units) and 1 ng of template DNA (all PCR reagents were purchased from TaKaRa, 216

Dalian, China). The PCR products were separated by agarose gel electrophoresis and 217

purified using the QIA quick Gel Extraction Kits (Qiagen, Hilden, Germany) and 218

sequenced on the ABI PRISM 3730 sequencer. 219

The determined 16S rRNA gene sequences were compared with the 220

GenBank/EMBL/DDBJ databases by using the BLASTN (1) search program. A 221

phylogenetic tree was constructed with the neighbour-joining (71) method using the 222

software package MEGA 3.1 (46) after pairwise alignments using the CLUSTAL_X 223

1.8 program (80). The stability of relationships was assessed by performing bootstrap 224

analyses (28) of the neighbour-joining data based on 1000 resamplings. DNA 225

sequences were deposited to GenBank and the Accession numbers were shown in 226

Table 3. 227

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Detection of PKS-I, PKS-ⅡⅡⅡⅡand NRPS sequences 228

Three sets of degenerate primers for the amplification of genes encoding polyketide 229

synthases (PKS-І, PKS-Ⅱ) and nonribosomal peptide synthetase (NRPS) from the 230

tested isolates were carried out as recommended by Ayuso-Sacido and Genilloud (4) 231

and Ketela et al. (45) (Table 2). The reaction mixture contained 2.5 units of Taq DNA 232

polymerase, 1 mM MgCl2, 0.4 mM dNTPs, 2 µM of each primer and 5% DMSO in a 233

50 µl reaction volume. Control reactions, without the actinobacterial DNA template. 234

Thermocycling conditions consisted of one denaturation step of 94°C for 5 min 235

followed by 30 amplification cycles of 94°C for 1 min, 57°C (for K1F/M6R, 236

A3F/A7R) or 58°C (for KSα/ KSβ) for 1 min, 72°C for 2 min followed by a final 237

extension at 72°C for 5 min. 238

239

Fermentation, extraction and evaluation of the antimicrobial activity 240

Each isolate was cultured in soybean mannitol liquid medium [soybean flour 12 g 241

and mannitol 20 g in 1000 ml tap water (pH 7.2–7.4)] at 28°C and shaked at 180 242

rev/min). After 7-12 days of cultivation, the fermentation broth was extracted with 243

ethanol. Each organic solvent extract was then evaporated under reduced pressure to 244

yield an ethanol extract. The ethanol extracts were then used for the antimicrobial 245

activity screening. The inhibitory effect of the extract obtained from endophytic 246

actinobacteria was tested using the paper disk (7 mm diameter) assay method (59). 247

25µl of ethanol extract suspension were pipetted onto each disc and incubated at 37°C, 248

followed by measurement of the diameters of the inhibition zone after 24 h. 25µl 249

ethanol was used as the control. Pathogenic bacterial organisms Staphylococcus 250

aureus, Bacillus subtilis, Pseudomonas aeruginosa and yeast Candida albicans were 251

used as indicator organisms to determine the antimicrobial activity. The pathogenic 252

microorganisms were deposited in the Yunnan institute of microbiology, Yunnan 253

University. 254

Results and Discussion 255

Evaluation of surface sterilization protocol 256

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Surface sterilization is important for studying endophytes. Imprinted agar of ISP 2 257

plate from each surface-sterilized sample showed no microbial growth after 15 days 258

incubation at 28°C. In addition, ISP 2 agar plates spread with the last washing water 259

from plant samples also did not emerge colonies of microorganisms after two weeks 260

incubation. This indicated that the five steps surface sterilization protocol was 261

effective to kill the epiphytic microorganisms. Thus the subsequent isolates can be 262

considered as true endophytic actinobacteria. 263

A 2.5% sodium thiosulfate solution was used instead of sterilized water rinses in 264

this study in order to remove the chlorine cover left on the plants surface by 265

hypochlorite disinfection. This was based on the consideration that even though plant 266

tissues were rinsed thoroughly with sterilized water after treated with NaOCl, there 267

were still toxic compounds present on their surfaces, which may kill endophytes or at 268

least stressed them so much that they were unable to form colonies on the plates. By 269

our tentative experiments, the increase in the number of CFU was indeed obvious 270

compared to the control (supplementary Table S1). This was consistent with the result 271

of the effects of rice seed surface sterilization with 2.0% sodium thiosulfate instead of 272

water rinses (60), and the fact that thiosulfate can suppress the detrimental effects of 273

hypochlorite on skin (34). It is also known that the alkaline environment favors the 274

growth of actinomycetes but not for endophytic fungi. The growth of fungal 275

endophyte was effectively inhibited by soaking the plant tissues in 10% NaHCO3 276

solution in our study so that the actinobacterial endophytes could grow out of tissues 277

before fungi overgrow the samples and mask the actinobacteria. The present surface 278

sterilization method was effective to help us acquire endophytic actinobacteria. 279

280

Selective isolation of culturable endophytic actinobacteria from medicinal plants 281

On the basis of characteristic colonial morphology, notably the ability to form 282

aerial hyphae and substrate mycelia, organisms putatively identified as actinobacteria 283

were selected. In total, 2174 actinobacterial strains were isolated from nearly 90 284

selected plant samples. According to the preliminary morphological identification, the 285

most abundant genus was Streptomyces (87%), which was consistent with the other 286

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reports from different hosts (10, 18, 83). As the aim of our study was to isolate 287

non-Streptomyces rare actinobacterial genera, according to the morphological criteria, 288

280 strains that did not seem to belong to Streptomyces or in doubt were further 289

checked for cultural, micromorphological characteristics and examined for the 290

presence of isomers of diaminopimelic acid. Based on these results, Pseudonocardia 291

was the dominant genus (57%), followed by Nocardiopsis spp. (8.3%), 292

Micromonospora spp. (6.4%), Streptosporangium spp. (3.8%) and others (24.5%) that 293

could not be accurately identified to the genus level. Except for Pseudonocardia, the 294

genera Micromonospora, Streptosporangium and Nocardiopsis were also reported 295

frequently from a wide range of host plants, such as maize, lichens and wheat (2, 31, 296

33). Then, 46 representative strains of each group were subjected to 16S rRNA gene 297

sequence analysis. 298

We used several isolation procedures in this study in order to get endophytic 299

actinobacteria as much as possible. Compared to previous commonly used 300

pretreatment methods for isolating endophytic actinobacteria of cutting samples into 301

small pieces about 0.2×0.5cm (11, 83), method 1 enlarged the colonization area of 302

samples onto the plates agar, which could be helpful for recovering endophytes. 303

We used the combined calcium carbonate enrichment, rehydration and 304

centrifugation (RC) pretreatment procedure developed earlier in method 2. This 305

method allowed efficient isolation of Dactylosporangium, Kineosporia, Kineococcus, 306

Herbidospora, Jiangella and Promicromonospora species. Although at present the 307

precise rationale behind the calcium carbonate effect is not clear, it seems plausible 308

that it might involve the following effects: the pH of the isolation sources after mixing 309

with powdered calcium carbonate would be altered in favor of the growth of 310

actinomycete propagules (82); calcium ions have the ability of stimulating the 311

formation of aerial mycelia by several actinomycete cultures (62). Previous isolation 312

of soil samples with calcium carbonate have demonstrated significantly increase of 313

the relative plate counts of actinomycete population (82). The centrifugation stage 314

greatly eliminated streptomycetes and other non-motile actinomycetes from the liquid 315

phase, thereby facilitating selective growth of rare, especially motile actinomycetes on 316

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the isolation plates subsequent to inoculation (39). Depending on the combined 317

calcium carbonate and RC procedures, Otoguro et al. (66) have successfully isolated 318

diverse Actinokineospora spp and other actinomycetes from soils and plant litters. Our 319

present study demonstrated that the enrichment stages with calcium carbonate and RC 320

procedure were also suitable for isolation zoosporic and other rare actinobacteria from 321

endophytic habitats. 322

Pretreatment method 3 was especially useful for isolating endophytic actinobacteria. 323

Besides the predominant Streptomyces, Pseudonocardia, Nocardiopsis and 324

Micromonospora species, other genera, including Amycolatopsis, Nocardia, 325

Nonomuraea, Actinomadura, Gordonia, Promicromonospora and Mycobacterium 326

were also recovered. This procedure was based on the fact that endophytic bacteria 327

reside in plant tissues mainly in intercellular spaces, rarely in intracellular spaces and 328

inside vascular tissues (79). By mild treatment with enzymes hydrolyzing plant cell 329

walls and subsequent differential centrifugation, most of the microbes associating 330

with plant tissues were collected and simultaneously to maintain the microbial cells 331

intact, which could be demonstrated by scanning electron microscopy (24). 332

Centrifugation is commonly used to collect the intercellular (apoplastic) fluid of plant 333

tissue (9, 23), and also has been successfully applied for the isolation of endophytic 334

bacteria from sugarcane stems by 3000 g force (24). This method seems to be 335

time-consuming, requiring both surface sterilisation and centrifugation, but several 336

samples can be centrifuged at the same time. It was first successfully applied to the 337

culture isolation of diverse endophytic actinobacteria in our study. Recently, Wang et 338

al. (85) reported the diversity of uncultured plant-associated microbes by improved 339

DNA extraction method and increased differential centrifugation at 5000 g force, 340

actinobacteria were the most dominant microbial group, covering 37.7% in the 16S 341

rRNA gene library, which also demonstrated the feasibility and prospect of 342

pretreatment method 3 to be used for isolating endophytic actinobacteria. 343

Actinobacteria were isolated on all of the 11 selective isolation media. 344

Observations on the isolation frequency from method 1 suggested that most strains 345

were isolated from the relative simple nutrient media, such as TWYE, sodium 346

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propionate agar and HV, which were most effective for isolation of endophytic 347

actinobacteria. However, other media seemed to be less suitable, due to the fact that 348

its high nutrient concentration allowed fast growing bacteria to overgrow slower 349

growing actinobacteria. This was consistent with the result from Coombs and Franco 350

(18). It is interesting that the ISP 5, raffinose–histidine agar, trehalose-proline agar 351

and our designed sodium propionate, cellulose-proline and xylan-arginine media are 352

more effective for isolation from procedures 2 and 3. Much more total number of 353

colonies formed on these media than others (data not shown). Cirousse et al. (16) 354

have detected asparagine as the main amino acid (70%) in the phloem sap of alfalfa. 355

Additionally, Mazzafera and Goncalves (58) found in the xylem sap of coffee that 356

almost 90% of the nitrogen in the form of amino acids was represented by asparagine 357

and glutamine. Similar results were reported from Tejera et al. (78) that predominant 358

nitrogen compounds in the apoplastic sap of sugarcane stem were amino acids 359

(50–70% of N), including serine, proline, alanine and aspartic acid. These facts 360

reminded us of attempting to use amino acids as nitrogen sources for culture isolation 361

plausibly, nevertheless, the real principle for isolation and role of these substances in 362

relationship with the establishment of the symbiosis of endophytes need further 363

experimental analysis. 364

Diversity of endophytic actinobacteria by 16S rRNA gene analysis 365

The endophytic actinobacteria isolated in this study displayed considerable 366

diversity, which distributed under 10 suborders: Pseudonocardineae (8 strains), 367

Corynebacterineae (8 strains), Streptomycineae (2 strains), Frankineae (1 strain), 368

Micromonosporineae (5 strains), Kineosporiineae (2 strains), Micrococcineae (8 369

strains), Streptosporangineae (8 strains), Propionibacterineae (1 strain) and 370

Glycomycineae (3 strains) within the class Actinobacteria in the phylogenetic tree 371

(Fig. S1) including 32 genera and more than 40 species. Notably, some uncommon 372

genera from endophytic environment, such as Amycolatopsis, Lentzea, 373

Pseudonocardia, Rhodococcus, Nocardia, Tsukamurella, Mycobacterium, Dietzia, 374

Gordonia, Dactylosporangium, Kineosporia, Janibacter, Kineococcus, Arthrobacter, 375

Micrococcus, Nonomuraea, Herbidospora and Glycomyces were discovered from 376

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present study. The percentage of 16S rRNA gene sequence similarities (97.2-100%) 377

of these isolates to the closest type strains was presented in Table 3. As shown in 378

Table 4, 34 out of the 46 strains were isolated from woody plants and most of them 379

were from roots (20 isolates) and stems (14 isolates), although the detailed taxa of 380

strains had no corresponding relationships with the taxonomic affiliations (species, 381

genera, families) of host plants. 382

Further phylogenetic analyses of part isolates were shown in Fig. S2a-e. Pairwise 383

comparison of the 16S rRNA gene sequences from the three Pseudonocardia isolates 384

(YIM 56035, YIM 56051 and YIM 61043) showed relatively high similarities (98.4, 385

97.5 and 98.6%) to the type strains P. kongjuensis, P. antarctica and P. zijingensis. 386

However, the phylogenetic analysis indicated that they were diversely distributed 387

within this genus and clustered singly in the phylogenetic tree (Fig. S2a), suggesting 388

that isolates YIM 56035, YIM 56051 and YIM 61043 might belong to new species. 389

The Saccharopolyspora isolates (YIM 65359, YIM 61095 and YIM 60513) had 390

lineages that were distinct from each other and from members of the genus and 391

formed distinct subclades in the tree supported by high bootstrap values (Fig. S2b). 392

Strain YIM 61095 has been characterized as a new species of this genus (68). 16S 393

rRNA gene sequences from YIM 65359 and YIM 60513 showed 98.4% and 99.1% 394

identity to the nearest neighbours YIM 61095 and Saccharopolyspora gregorii, 395

respectively. DNA-DNA hybridizations, phenotypic comparisons and 396

chemotaxonomic analysis classified YIM 65359 and YIM 60513 as new species of 397

the genus Saccharopolyspora. The Glycomyces isolates (YIM 56134, YIM 61331 and 398

YIM 56256) formed distinct clusters within the Glycomyces 16S rRNA gene tree (Fig. 399

S2c), although shared highest 16S rRNA gene similarities within the range 98.9, 98.7 400

and 99.7% to the closest recognized strains. All the three isolates have been identified 401

as three different new species of the genus Glycomyces (67, 69). Although the 16S 402

rRNA gene sequences from two isolates, YIM 61515 and 56864 showed up to 99.0% 403

and 99.4% identity to the related type strains of the genus Promicromonospora (Fig. S 404

2d), DNA-DNA relatedness values (unpublished) were well below the 70% cut-off 405

point recommended by Wayne et al. (86) for the delineation of strains that belong to 406

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the same genomic species, indicating that they are still new species. It was particular 407

interesting to recover isolate YIM 61359. Comparison of the 16S rRNA gene 408

sequences of this isolate and the closest neighbours indicated that this strain was 409

closely related to the type strains of the genera Micromonospora (96.6%-98.1%, 410

similarity), Salinispora (97.7%, similarity) and Polymorphospora rubra (97.6%, 411

similarity). However, it formed a distinct monophyletic clade within the family 412

Micromonosporaceae (Fig. S2e) in the phylogenetic tree, most closely related to the 413

first obligate new marine actinomycete genus Salinispora, which produced antibiotic 414

Salinosporamide A (27, 56). This indicated that isolate YIM 61359 should represent a 415

new genus proposed as ‘Plantactinospora gen. nov’ of the family 416

Micromonosporaceae and merit secondary metabolites research. Although the isolates 417

YIM 65003 (Rhodococcus), YIM 65001 (Dietzia), YIM 65002 (Dietzia), YIM 60475 418

(Streptomyces), YIM 65188 (Streptomyces), YIM 56238 (Micrococcus) and YIM 419

61503 (Jiangella) had more than 97% 16S rRNA gene sequences similarities to the 420

nearest type strains respectively, they have already been identified as new species (14, 421

15, 49, 51, 52, 70) by using the polyphasic taxonomic analyses. Detailed 422

characterizations of other isolates are currently being done, in comparison with the 423

nearest type strains to determine whether they are new species. Taxonomic 424

description of these putative novel species will be further characterized elsewhere. 425

We isolated and cultured 46 representatives of 32 genera of actinobacteria from 426

medicinal plants. This is the first report to recover such a high diversity of culturable 427

actinobacteria from endophytic environments. In addition, to our knowledge, this is 428

the first time that strains of the rarely recovered genera Saccharopolyspora, Dietzia, 429

Blastococcus, Dactylosporangium, Promicromonospora, Oerskovia, Actinocorallia 430

and Jiangella have been isolated and cultured from the inner parts of plants. 431

Taechowisan et al. (76) isolated 330 isolates belonging to 4 different genera 432

(Streptomyces, Microbispora, Nocardia and Micromonospora) from 36 medicinal 433

plant species from Thailand. Tan et al. (77) found 619 actinomycetes isolated from 434

different cultivars of tomato, and all of them were Streptomyces spp. Recently, Lee et 435

al. (48) isolated 8 endophytic actinobacterial genera in only 81 isolates of Chinese 436

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cabbage roots, and Microbispora spp. (67%) were the most common isolates, 437

followed by Streptomyces spp. (12%) and Micromonospora spp. (11%). Obviously, 438

the actinobacterial richness and diversity from tropical rainforest in Xishuangbanna of 439

our present study is much higher comparison with other reports, and tropical 440

rainforest have potential as excellent source of actinobacteria and new species. 441

Therefore, it seems clear that endophytic communities are diverse and the extent of 442

diversity may vary between different sample collection regions and different plant 443

species, the diversity of isolated actinobacteria was largely dependent on the isolation 444

methods. 445

446

Antimicrobial activity and detection of the PKS and NRPS genes in the selected 447

actinobacteria 448

All the 46 isolates were tested against pathogenic bacteria Staphylococcus aureus, 449

Bacillus subtilis, Pseudomonas aeruginosa and yeast Candida albicans to evaluate 450

their production of antimicrobial activities. 24 out of 46 isolates (52.2%) exhibited 451

activity against at least one tested pathogenic microorganism. Activity against B. 452

subtilis was clearly the most frequent (12 isolates, 26.1%). Activity against P. 453

aeruginosa was the least frequent (10.9%), while 19.6% and 17.4% of the isolates 454

were active against S. aureus and C. albicans. Six isolates were found to inhibit two 455

pathogens. Two isolates, YIM 61515 and YIM 61333 appeared to have a broad 456

spectrum of antimicrobial activity. Four isolates, YIM 61341, YIM 61333, YIM 457

61105 and YIM 56134 exhibited relatively strong inhibitory effect against pathogenic 458

microorganisms C. albicans, S. aureus and P. aeruginosa. The strong inhibitory 459

activities of these strains against a variety of pathogens suggested that these 460

endophytic actinobacteria may be potential candidates for the production of bioactive 461

compounds. Chemical analysis of some of the strains is currently being carried out in 462

order to identify active compounds and to assess their novelty. 463

The 46 strains were screened for the presence of PKS-І, PKS-Ⅱ and NRPS 464

sequences by specific amplification of chromosomal DNA with the primers K1F/M6R, 465

KSα/ KSβ and A3F/A7R, respectively (Table 5) to evaluate the biosynthetic potential 466

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in terms of natural product drug discovery. NRPS sequences were detected in 12 467

isolates (26.1%) whereas PKS-І and PKS-Ⅱsequences were detected in only five and 468

seven out of the 46 strains (10.9% and 15.2%). Strains YIM 65293 and YIM 65377 469

gave positive amplification products with both the PKS-Ⅱ and NRPS primers. Both 470

PKS-І and NRPS gene sequences were amplified from strain YIM 61441. All the 471

three target genes were detected in strain YIM 61375. Several representative PKS-І, 472

PKS-Ⅱ and NRPS gene amplified products were cloned, sequenced, and their 473

subsequent analysis confirmed that they indeed encode parts of the expected 474

biosynthetic enzymes (see accession no. FJ615259). 475

The results of antimicrobial activity and the detection of functional genes seemed to 476

have no direct correlations in present study. Several isolates, such as YIM 61095 and 477

YIM 65377 had no antimicrobial activity, but could be successfully amplified target 478

genes. 28 strains (60.9%) were not detected the PKS and NRPS genes using the 479

selected degenerate primer pairs, which have been used in a broad survey of these 480

genes in a similar study (4). The absence of amplification products from some of the 481

strains may reflect the lack of PKS-І, PKS-Ⅱ and NRPS genes, though it is also 482

possible that these specific degenerate primer pairs might not be suitable to amplify 483

these genes. Furthermore, not all NRPS genes are involved in the biosynthesis of 484

bioactive secondary metabolites; indeed, the products of such genes may be involved 485

in functions such as iron metabolism or quorum sensing (30). It is also possible that 486

the genes detected by PCR are nonfunctional. Nevertheless, the strategy of 487

prescreening with PCR primers, targeting genes encoding the biosynthesis of 488

bioactive compounds is an effective approach for detecting novel and useful 489

secondary metabolites (19, 32, 41, 45). 490

491

Conclusions 492

In summary, this study demonstrates that an unexpected diversity of actinobacteria 493

colonize the interior of medicinal plants in Xishuangbanna tropical rainforests and 494

suggests that these strains might represent a valuable source of new species and 495

biological active compounds with antimicrobial activity and genes for their 496

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biosynthesis. The isolation procedure is critical and important step in studies on 497

endophytic actinobacteria. It is indeed need to improve traditional selective isolation 498

methods to recover the untapped majority of endophytic actinobacteria. Although 499

many questions remain to be answered regarding to the ecological function of 500

actinobacteria in the endophytic environment as well as their evolution and 501

biogeographic distribution. The increasing numbers of rare actinobacteria isolated 502

from medicinal plants indicate that plants are potentially unique sources of novel 503

actinobacteria with promising potential to produce highly bioactive metabolites and 504

their potential should not be overlooked. 505

506

507

Acknowledgments 508

This research was supported by National Basic Research Program of China (Project 509

no. 2004CB719601). W.-J. Li was supported by Program for New Century Excellent 510

Talents in University. 511

512

513

514

515

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mycelium formation in actinomycetes. J. Antibiot. 42: 440-447. 711

63. Nejad, P., and P. A. Johnson. 2000. Endophytic bacteria induce growth 712

promotion and wilt disease suppression in oilseed rape and tomato. Biological. 713

Control. 18: 208–215. 714

64. NIAID. 2001. NIAID Global Health Research Plan for HIV/AIDS, Malaria and 715

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65. Oldfield, C., N. T. Wood, S. C. Gilbert, F. D. Murray, and F. R. Faure.1998. 717

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organisms belonging to the genus Rhodococcus, and related taxa. Antonie. Van. 719

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67. Qin, S., H. H. Chen, H. P. Klenk, G. Z. Zhao, J. Li, L. H. Xu, and W. J. Li. 724

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from two medicinal plants in China. Int. J. Syst. Evol. Microbiol. 59: 1023-1027. 726

68. Qin, S., J. Li, G. Z. Zhao, H. H. Chen, L. H. Xu, and W. J. Li. 2008. 727

Saccharopolyspora endophytica sp. nov., an endophytic actinomycete isolated 728

from the root of Maytenus austroyunnanensis. Syst. Appl. Microbiol. 31: 352-357. 729

69. Qin, S., H. B. Wang, H. H. Chen, Y. Q. Zhang, C. L. Jiang, L. H. Xu, and W. J. 730

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70. Qin, S., G. Z. Zhao, J. Li, W. Y. Zhu, L. H. Xu, and W. J. Li. 2008. Jiangella 733

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71. Saitou, N., and M. Nei. 1987. The neighbor-joining method: a new method for 736

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72. Sessitsch, A., B. Reiter, and G. Berg. 2004. Endophytic bacterial communities of 738

field-grown potato plants and their plant-growth promoting and antagonistic 739

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73. Shirling, E. B., and D. Gottlieb. 1966. Methods for characterization of 741

Streptomyces species. Int. J. Syst. Bacteriol. 16: 313–340. 742

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Phytopathology. 50: 88-89. 769

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Isolation, Diversity, and Anti-microbial Activity. Microbiol. Ecol. 57: 749-756. 772

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Evol. Microbiol. 37: 463–464. 784

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and G. A. Strobel. 2007. Bioactive endophytic streptomycetes from the Malay 792

Peninsula. FEMS Microbiol. Lett. 274: 83–88. 793

794

795

796

797

798

799

800

801

802

803

804

805

806

807

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Table 1. Compositions of the 11 different media for isolation of endophytic 808

actinobacteria from plant samples. 809

810

Media Compositions References

M1 TWYE 21

M2 modified TWYE supplemented with plant extract This study

M3 glycerol-asparagine agar (ISP 5) 73

M4 HV agar 40

M5 inorganic salts-starch agar (ISP 4) 73

M6 YIM 38 medium (4.0 g malt extract, 4.0 g yeast extract, 4.0 g glucose, vitamin

mixture and agar 15.0g

This study

M7 raffinose–histidine agar 84

M8 sodium propionate agar (sodium propionate 1.0g, L-asparagine 0.2 g, KH2PO4 0.9

g, K2HPO4 0.6 g, MgSO4·7H2O 0.1 g, CaCl2·2H2O 0.2 g, agar 15.0g)

This study

M9

cellulose-proline agar (cellulose, 2.5g, sodium pyruvate 2.0g, KNO3 0.25g, proline

1.0g, MgSO4˙7H2O 0.2g, K2HPO4 0.2g, CaCl2 0.5g, FeSO4˙7H2O 10mg and agar

15.0g)

This study

M10 trehalose-proline medium (fucose 5.0 g, proline1.0 g, (NH4)2SO4 1.0 g, NaCl 1.0

g, CaCl2 2.0 g, K2HPO4 1.0 g, MgSO4·7H2O 1.0 g, agar 15.0g)

This study

M11 xylan-arginine agar (xylan 2.5g, arginine1.0g, (NH4)2SO4 1.0g, CaCl2 2.0g,

K2HPO4 1.0g, MgSO4·7H2O 0.2g, FeSO4˙7H2O 10mg and agar 15.0g)

This study

811

812

813

814

815

816

817

818

819

820

821

822

823

824

825

826

827

828

829

830

831

832

833

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Table 2. Polymerase chain reaction (PCR) primers used in this study. 834

835

Primers

name

Sequences (5’-3’) Target

genes

Length of the target

gene fragments (bp)

Reference

PA 5′-AGAGTTTGATCCTGGCTCAG-3′ 16S rRNA 1400-1500 22

PB 5′-AAGGAGGTGATCCAGCCGCA-3′

K1F 5'-TSAAGTCSAACATCGGBCA-3' PKS-І 1200-1400 4

M6R 5'-CGCAGGTTSCSGTACCAGTA-3'

KSα 5'-TSGCSTGCTTGGAYGCSATC-3' PKS-Ⅱ 600 45

KSβ 5'-TGG AANCCG CCGAABCCTCT-3'

A3F 5'-GCSTACSYSATSTACACSTCSGG-3' NRPS 700-800

A7R 5'-SASGTCVCCSGTSCGGTAS-3' 4

836

837

838

839

840

841

842

843

844

845

846

847

848

849

850

851

852

853

854

855

856

Table 3. Actinobacteria isolated from different organs of host plants using three 857

different methods, with taxonomic status of plants and similarity values of 16S rRNA 858

gene sequences. 859

860

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Isolates

(GenBank accession no.)

Host plants (species) Taxonomic status

(family, genus) of host plants

Organs Closest cultivated species Similarity

(%)

Isolation

methods

YIM 61095 (EU814512) Maytenus austroyunnanensis Celastraceae, Maytenus Root Saccharopolyspora flava AS 4.1520T (AF154128) 97.7 1

a

YIM 65359 (FJ214364) Tripterygium hypoglaucum Celastraceae, Tripterygium Stem Saccharopolyspora flava AS 4.1520T (AF154128) 98.4 1

YIM 60513 (EU005371) Gloriosa superba Liliaceae, Gloriosa Stem Saccharopolyspora gregorii NCIB 12823T (X76962) 99.1 1

YIM 65085 (FJ214357) Osyris wightiana Santalaceae, Osyris Root Amycolatopsis pretoriensis NRRL B-24133 T

(AY183356) 98.0 3

YIM 65117 (FJ214358) Ficus tikoua Moraceae, Ficus Root Lentzea albida IFO 16102 T

(AB006176) 99.1 1

YIM 61043 (FJ214340) Maytenus austroyunnanensis Celastraceae, Maytenus Root Pseudonocardia zijingensis JCM 11117T (AF325725) 98.6 3

YIM 56051 (EU200680) Callicarpa longifolia Verbenaceae, Callicarpa Leaf Pseudonocardia alni IMSNU 20049T (AJ252823) 97.5 1

YIM 56035 (DQ887489) Lobelia clavata Campanulaceae, Lobelia Leaf Pseudonocardia kongjuensis DSM 44525T (AJ252833) 98.4 1

YIM 65003 (EU325542) Cercidiphyllum japonicum Cercidiphyllaceae, Cercidiphyllum Leaf Rhodococcus fascians DSM 20669T (X79186) 99.6 1

YIM 61441 (FJ214349) Maytenus austroyunnanensis Celastraceae, Maytenus Root Nocardia carnea DSM 46071T (AF430037) 98.3 3

YIM 61394 (FJ214346) Maytenus austroyunnanensis Celastraceae, Maytenus Stem Tsukamurella tyrosinosolvens DSM 44234T (AY238514) 99.9 2

b

YIM 65220 (FJ214359) Paris yunnanensis Liliaceae, Paris Leaf Mycobacterium monacense B9-21-178T (AF107039) 97.2 3

c

YIM 65001 (EU375845) Schima sp. Theaceae, Schima Stem Dietzia maris DSM 43672T (X79290) 99.8 1

YIM 65002 (EU375846) Cercidiphyllum japonicum Cercidiphyllaceae, Cercidiphyllum Root Dietzia natronolimnaea 15LN1T (X92157) 99.5 1

YIM 61527 (FJ214354) Maytenus austroyunnanensis Celastraceae, Maytenus Stem Gordonia sputi DSM 43896T (X80634) 99.0 3

YIM 61401 (FJ214347) Maytenus austroyunnanensis Celastraceae, Maytenus Stem Gordonia polyisoprenivorans W8130T (DQ385609) 97.9 3

YIM 60475 (EU200683) Maytenus austroyunnanensis Celastraceae, Maytenus Root Streptomyces hainanensis YIM 47672T (AM398645) 99.2 1

YIM 65188 (EU925562) Sedum sp. Crassulaceae, Sedum Root Streptomyces special GW 41-1564T (AM934703) 97.5 1

YIM 65287 (FJ214361) Tripterygium wilfordii Celastraceae, Tripterygium Root Blastococcus aggregatus DSM 4725T (AJ430193) 99.6 1

YIM 61359 (FJ214343) Maytenus austroyunnanensis Celastraceae, Maytenus Root Polymorphospora rubra DSM 44947T (AB223089) 97.6 2

YIM 65312 (FJ214363) Tripterygium wilfordii Celastraceae, Tripterygium Root Dactylosporangium aurantiacum DSM 43157T (X93191) 98.0 2

YIM 65268 (FJ214360) Berberis chingii Berberidaceae, Berberis Stem Catellatospora chokoriensis 2-25(1)T (AB200231) 99.0 1

YIM 61481 (FJ214350) Maytenus austroyunnanensis Celastraceae, Maytenus Leaf Micromonospora narashino DSM 43172T (X92602) 99.3 3

YIM 61363 (FJ214344) Maytenus austroyunnanensis Celastraceae, Maytenus Leaf Micromonospora peucetia DSM 43363 T

(X92603) 98.0 1

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YIM 65293 (FJ214362) Tripterygium wilfordii Celastraceae, Tripterygium Stem Kineosporia aurantiaca IFO 14067T (D86937) 98.2 1

YIM 65377 (FJ214365) Tripterygium wilfordii Celastraceae, Tripterygium Stem Kineococcus aurantiacus IFO 15268T (X77958) 98.0 2

YIM 61515 (FJ214352) Maytenus austroyunnanensis Celastraceae, Maytenus Leaf Promicromonospora aerolata IFO 16526T (AJ487303) 99.0 3

YIM 56864 (EU200679) Cymbopogon citratus Poaceae, Cymbopogon Root Promicromonospora sukumoe DSM 44121T (AJ272024) 99.4 2

YIM 60535 (EU200684) Ginkgo sp. Ginkgoaceae, Ginkgo Leaf Oerskovia jenensis DSM 46097T (AJ314850) 99.3 1

YIM 61525 (FJ214353) Maytenus austroyunnanensis Celastraceae, Maytenus Root Janibacter melonis KCTC 9987T (AY522568) 99.8 1

YIM 61410 (FJ214348) Maytenus austroyunnanensis Celastraceae, Maytenus Stem Microbacterium paraoxydans H110bT (EF204432) 100 3

YIM 61510 (FJ214351) Maytenus austroyunnanensis Celastraceae, Maytenus Leaf Arthrobacter mysorens LMG 16219T (AJ639831) 98.2 3

YIM 65004 (FJ214355) Polyspora axillaris Theaceae, Polyspora Root Micrococcus flavus CGMCC 1.5361T (DQ491453) 99.7 1

YIM 56238 (EU005372) Aquilaria sinensis Thymelaeaceae, Aquilaria Root Micrococcus flavus CGMCC 1.5361T (DQ491453) 99.0 1

YIM 61341 (FJ214342) Maytenus austroyunnanensis Celastraceae, Maytenus Stem Nocardiopsis dassonvillei JPL-3T (AY030320) 98.4 1

YIM 61333 (FJ214341) Maytenus austroyunnanensis Celastraceae, Maytenus Root Nocardiopsis dassonvillei JPL-3T (AY030320) 98.2 3

YIM 56155 (FJ214339) Duranta repens Linn Verbenaceae, Duranta Root Actinocorallia aurantiaca JCM 8201T (AF134066) 99.1 2

YIM 60542 (EU005370) Millettia reticulata Papilionaceae, Millettia Leaf Actinocorallia herbida IFO 15485T (D85473) 99.1 2

YIM 61435 (FJ157185) Maytenus austroyunnanensis Celastraceae, Maytenus Leaf Actinomadura atramentaria DSM 43919T (AJ420138) 97.4 2

YIM 61375 (FJ214345) Maytenus austroyunnanensis Celastraceae, Maytenus Stem Streptosporangium vulgare DSM 44112T (X89957) 97.4 2

YIM 61105 (FJ157184) Maytenus austroyunnanensis Celastraceae, Maytenus Leaf Nonomuraea candida DSM 45086T (DQ285421) 98.2 1

YIM 65070 (FJ214356) Osyris wightiana Santalaceae, Osyris Stem Herbidospora cretacea IFO 15474T (D85485) 99.5 2

YIM 61503 (FJ157186) Maytenus austroyunnanensis Celastraceae, Maytenus Stem Jiangella alkaliphila DSM 45079T (AM422451) 98.8 2

YIM 56134 (EU200681) Carex baccans Nees Cyperaceae, Carex Root Glycomyces algeriensis NRRL B-16327T (AY462044) 98.9 1

YIM 56256 (EU200682) Scoparia dulcis Scrophulariaceae, Scoparia Root Glycomyces sambucus DSM 45047T (DQ460469) 99.7 1

YIM 61331 (EU814511) Maytenus austroyunnanensis Celastraceae, Maytenus Root Glycomyces sambucus DSM 45047T (DQ460469) 98.7 1

a Samples were aseptically crumbled into small fragments and directly placed on the selective media and incubated at 28 ºC for 2-8 weeks. 861

b Combined calcium carbonate enrichment, rehydration and centrifugation (RC) 862

c Combined enzymatic hydrolysis and differential centrifugation method. 863

864

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Table 4. Statistical analyses on the relationships between taxonomic status of the 46 865

endophytic actinobacterial strains associated with particular plant organs and taxa of 866

plant samples. 867

Taxonomic status of isolates Plants Organs Isolates

no. Suborder Family Genus

Roots

7

Pseudonocardineae

Streptomycineae

Micrococcineae

Streptosporangineae

Glycomycineae

Pseudonocardiaceae

Streptomycetaceae

Promicromonosporaceae

Thermomonosporaceae

Glycomycetaceae

Amycolatopsis,

Lentze, Glycomyces

Pseudonocardia

Streptomyces

Promicromonospora

Actinocorallia

Stems 2 Pseudonocardineae

Streptosporangineae

Pseudonocardiaceae

Streptosporangiaceae

Saccharopolyspora

Herbidospora

Leaves 3 Pseudonocardineae

Corynebacterineae

Pseudonocardiaceae

Mycobacteriaceae

Pseudonocardia

Mycobacterium

Herbaceous

Total no. 12 6 7 10

Roots

13

Pseudonocardineae

Streptomycineae

Corynebacterineae

Frankineae

Micromonosporineae

Micrococcineae

Streptosporangineae

Glycomycineae

Pseudonocardiaceae

Streptomycetaceae

Dietziaceae

Nocardiaceae

Geodermatophilaceae

Micromonosporaceae

Intrasporangiaceae

Micrococcaceae

Nocardiopsaceae

Glycomycetaceae

Saccharopolyspora

Pseudonocardia,

Dietzia, Glycomyces

Streptomyces

Nocardi, Janibacter

Blastococcus

Dactylosporangium

Micrococcus

Nocardiopsis

‘Plantactinospora’

Stems

12

Pseudonocardineae

Corynebacterineae

Micromonosporineae

Kineosporiineae

Micrococcineae

Streptosporangineae

Propionibacterineae

Pseudonocardiaceae

Tsukamurellaceae

Dietziaceae

Nocardiaceae

Micromonosporaceae

Kineosporiaceae

Microbacteriaceae

Nocardiopsaceae

Streptosporangiaceae

Nocardioidaceae

Saccharopolyspora

Tsukamurella

Dietzia, Jiangella

Gordonia

Catellatospora

Kineosporia

Kineococcus

Microbacterium

Nocardiopsis

Streptosporangium

Leaves

9

Corynebacterineae

Streptosporangineae

Micrococcineae

Micromonosporineae

Nocardiaceae

Streptosporangiaceae

Thermomonosporaceae

Cellulomonadaceae

Promicromonosporaceae

Micromonosporaceae

Micrococcaceae

Rhodococcus

Nonomuraea

Actinomadura

Actinocorallia

Oerskovia

Promicromonospora

Micromonospora

Arthrobacter

Woody

Total no. 34 10 18 28

868

869

870

871

872

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Table 5. Antimicrobial activity and PKS/NRPS genes of culturable actinobacteria 873

from medicinal plants. 874

875

Isolate no. Candida

albicans

Staphylococcus

aureus

Bacillus

subtilis

Pseudomonas

aeruginosa

PKS-I PKS-Ⅱ NRPS

YIM 61095 - - - - - - +

YIM 65359 - - - - - - -

YIM 60513 - - - + + - -

YIM 65085 - - - - - - -

YIM 65117 - ++ ++ - - - +

YIM 61043 - + - - - - +

YIM 56051 - ++ - - - + -

YIM 56035 - - - - - + -

YIM 65003 - - - - - - +

YIM 61441 - - - - + - +

YIM 61394 - - - - - - -

YIM 65220 - + + - - + -

YIM 65001 - - - - - - -

YIM 65002 - - - - - - -

YIM 61527 + - + - - - -

YIM 61401 - - - - - - -

YIM 60475 - - ++ - - - -

YIM 65188 - - - - - - -

YIM 65287 - - - - - - -

YIM 61359 - ++ - ++ - - -

YIM 65312 - ++ - - - - -

YIM 65268 - - ++ - - + -

YIM 61481 ++ - - - - - +

YIM 61363 ++ - - - + - -

YIM 65293 - - + - - + +

YIM 65377 - - - - - + +

YIM 61515 - + ++ ++ - - -

YIM 56864 - - - ++ - - -

YIM 60535 - - - - - - -

YIM 61525 - - - - - - -

YIM 61410 + - - - - - -

YIM 61510 - - - - - - -

YIM 65004 - - - - - - -

YIM 56238 - - - - - - -

YIM 61341 +++ - ++ - - - +

YIM 61333 +++ - ++ +++ - - +

YIM 56155 - + - - - - -

YIM 60542 - - - - - - -

YIM 61435 - - - - - - -

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YIM 61375 ++ - - - + + +

YIM 61105 +++ - - - - - -

YIM 65070 - - ++ - - - +

YIM 61503 - - ++ - - - -

YIM 56134 - +++ + - + - -

YIM 56256 - - - - - - -

YIM 61331 - - - - - - -

The antimicrobial activity was estimated by measuring the diameter of the clear zone of growth 876

inhibition. Symbles: +, ++ and +++ indicate presence, moderate and strong activity, respectively. 877

878

879

880

881

882

883

884

885

886

887

888

889

890

891

892

893

894

895

896

897

898

899

900

901

902

903

904

905

906

907

908

909

910

911

912

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