Review Article Progress in Microbes and Molecular Biology A Review on Mangrove Actinobacterial Diversity: The Roles of Streptomyces and Novel Species Discovery Jodi Woan-Fei Law1,2, Priyia Pusparajah1, Nurul-Syakima Ab Mutalib3, Sunny Hei Wong4, Bey-Hing Goh5*, Learn-Han Lee1* 1Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Selangor Darul Ehsan, Malaysia 2Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, PR China 3UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, University Kebangsaan Malaysia, Kuala Lum- pur, Malaysia 4Li Ka Shing Institute of Health Sciences, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong 5Biofunctional Molecule Exploratory Research Group (BMEX), School of Pharmacy, Monash University Malaysia, Selangor Darul Ehsan, Malaysia Abstract : In the class Actinobacteria, the renowned genus Streptomyces comprised of a group of uniquely complex bacteria that capable of synthesizing a great variety of bioactive metabolites. Streptomycetes are noted to possess several special qual- ities such as multicellular life cycle and large linearized chromosomes. The significant contribution of Streptomyces in mi- crobial drug discovery as witnessed through the discovery of many important antibiotic drugs has undeniably encourage the exploration of these bacteria from different environments, especially the mangrove environments. This review emphasizes on the genus Streptomyces and reports on the diversity of actinobacterial population from mangroves at different regions of the world as well as discovery of mangrove-derived novel Streptomyces species. Overall, the research on diversity of Actinobac- teria in the mangrove environments remains limited. A total of 19 novel Streptomyces spp. isolated from mangroves between the year 2009 - early 2019, notably from China, India, Malaysia, and Thailand. Hence, it will be worthwhile to encourage the study of these bacteria from mangroves of different locations. Keywords: Streptomyces; actinobacteria; mangrove; environment; forest *Correspondence to: Learn-Han Lee, Jeffrey Cheah School of Medicine and Health Sciences, Monash Uni- versity Malaysia, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia. [email protected]; leelear- [email protected]; Bey-Hing Goh, School of Pharma- Received: 06th January 2019 cy, Monash University Malaysia, 47500 Bandar Sun- Accepted: 30th April 2019 way, Selangor Darul Ehsan, Malaysia. goh.bey.hing@ Published Online: 22nd May 2019 monash.edu Citation: Law JWF, Pusparajah P, Ab Mutalib NS, et al. A Review on Mangrove Actinobacterial Diversity: The Roles of Streptomyces and Novel Species Discovery. Prog Microbes Mol Biol 2019; 2(1): a0000024. INTRODUCTION including order Streptomycetales that contains only the family Streptomycetaceae, where the type genus Strep- tomyces within this family is undeniably one of the most The phylum Actinobacteria is among the earliest lineages extensively studied genera in the phylum Actinobacte- within the prokaryotes which appears to exist since 2.7 ria[5-7]. The class Actinobacteria can be categorized into [1] billion years ago . Being one of the major lineages in the two groups: (1) the Streptomyces which represents the domain Bacteria, this phylum consists of many genera dominant genus, and (2) the non-Streptomyces genera which contributed to its vast diversity with reference to (e.g. Sinomonas spp., Mumia spp., Microbacterium spp. the morphological and physiological variations as well etc.) which also known as rare Actinobacteria[8-13]. as metabolic abilities[2-4]. In the recent road map of phy- lum Actinobacteria revised by Ludwig et al. (2012)[5], The genus Streptomyces was first introduced by Profes- this phylum currently comprises 6 classes, namely “Ac- sor Dr. Selman Abraham Waksman and Professor Dr. tinobacteria”, “Nitriliruptoria”, “Acidimicrobiia”, “Co- Arthur Trautwein Henrici in the year 1943[14]. The name riobacteriia”, “Thermoleophilia”, and “Rubrobacteria”. Streptomyces means “twisted fungus” in Greek and it is The largest class “Actinobacteria” consists of 15 orders, given due to its morphology which appears to be simi- Copyright 2019 by Law JWF et al. and HH Publisher. This work under licensed under the Creative Commons Attribution-NonCom- mercial 4.0 International Lisence (CC-BY-NC 4.0) 1 A Review on Mangrove Actinobacterial... lar to that of filamentous fungi; Streptomyces is derived each will differentiate into resistant spores (reproductive from the combination of Actinomyces which means “ray sporulation phase) (Figure 1)[18,26,27]. According to the ob- fungus” in Greek and Streptothrix which means “twisted servation on agar plate media, the substrate mycelium of hair” in Greek[14,15]. This genus is made up of a group Streptomyces grows into and across the surface of agar of aerobic, Gram-positive, non-motile, and multicellular plate through extension and branching, whilst the aerial filamentous microorganisms that are commonly found in mycelium erected on top of the substrate mycelium that soil, often recognized as persistent soil saprophytes[16-19]. appears above the surface of agar plate with granular, Besides, most of the members of Streptomyces produce a powdery, floccose or velvety appearance[26,28]. Apparently, characteristic earthy odour due to the production of geos- the morphological differentiation event in Streptomyces is min[7,20]. This group of bacteria has been greatly explored related to the sensing of essential nutrients depletion[18,27]. for their pharmaceutically important natural antibiotics Meanwhile, Streptomyces starts to produce secondary or other bioactive compounds, and industrially useful en- metabolites when encountering nutritional deficiencies zymes[1,17,21]. As a result of the continuous efforts in isola- in a stressful environment and this process is referred tion and screening of Streptomyces for their biologically to physiological differentiation[29]. Therefore, there is active secondary metabolites, the genus Streptomyces a close association between morphological differentia- presently contains 848 species and 38 subspecies that are tion and physiological differentiation in the life cycle of validly identified (http://www.bacterio.net/streptomyces. Streptomyces. During the shifting phase from vegetative html, accessed on 15th January 2019)[22]. to aerial growth and sporulation, metabolic development is activated and thus many interesting secondary metabo- UNIQUE FEATURES OF Streptomyces lites are produced to ensure the survival of Streptomyces in stressful environments[27,29,30]. Furthermore, many of Streptomyces bacteria are uniquely complex microor- the Streptomyces isolates can produce diverse pigments ganisms, primarily well-known as prolific producers of or pigmented secondary metabolites that responsible for secondary metabolites with bioactivities such as antimi- the colour of substrate and aerial mycelia of Streptomyces crobial, anticancer, antioxidant, and immunosuppressive colonies on agar plate media[26,30]. activities[19,20,23,24]. Production of secondary metabolites is not essential for bacterial growth, but it is crucial to Another distinctive feature of Streptomyces is that mem- facilitate the defence mechanisms of the hosts as to en- bers of this genus have linearized chromosomes, com- sure survival during unfavourable environmental condi- monly with a large size of over 8 Mbp and a high G+C tions[6]. It is remarkable that streptomycetes can generate [32-34] secondary metabolites with various interesting bioactivi- content of approximately 67-78 mol % . In the year ties and extraordinary chemical diversity, although the 2002, the first complete genome sequence of Streptomy- roles play by these molecules in the survival of the host ces was reported - a model actinomycete, Streptomyces are still not fully understood other than the antibiotics coelicolor A3(2) with a genome size of 8,667,507 bp, which benefit the host by thwarting the growth of com- thus, became the largest completely sequenced bacterial [35] peting microbes in unfavourable environment[18,25]. genome at that moment . In the following year, the com- plete genome sequence of an industrial strain Streptomy- Actually, there are several notable features of Strepto- ces avermitilis was reported to consist of 9,025,608 bp[36]. myces that could account for their complex secondary Since then, many Streptomyces strains have been subject- metabolism. One of the unique features of streptomy- ed to whole genome sequencing to at least the draft stage cetes is their multicellular life cycle involving com- and these genome sequences are publicly available[37]. plex morphological changes. Upon spore germination, These evidences show that the genome size of Streptomy- they grow by tip extension and the development of a ces is at least almost two times larger as compared with network of branched filaments known as the substrate other well-studied bacteria such as Bacillus subtilis with mycelium (vegetative phase) is initiated. As they age, genome size of 4,214,810 bp, and Escherichia coli K-12 aerial multinucleated mycelium is formed which sub- with genome size of 4,639,221 bp[20,38,39]. The large ge- sequently experience synchronous cell division leading nome size correlates with the ability of Streptomyces to to the generation of monoploid compartments