Abstract
Genome mining in silico approaches allow scientists to proficiently evaluate the genomic potency of secondary bioactive chemical producers and find new bioactive compounds in different bacteria. Streptomyces is one of the most ubiquitous bacterial genera in the environments, and well-known as prolific producers of diverse and valuable natural products (NPs) with significant biological activities. Mining and prioritizing of NP biosynthetic gene clusters (BGCs) would be the most important stage in the identification of novel compounds. Comparative genomics and genetic similarity network analysis of 62 Streptomyces public reference genomes demonstrated that individuals of these species exhibit a huge number of distinct NP BGCs, the most of which are cryptic and unconnected to any reported NPs with high phylogenetic variation among individuals. It was assumed that substantial heterogeneity across the varieties of species of Streptomyces drives outstanding biosynthetic and metabolic potential, making them plausible candidates for the identification of novel molecules.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11274-022-03433-y/MediaObjects/11274_2022_3433_Fig1_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11274-022-03433-y/MediaObjects/11274_2022_3433_Fig2_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11274-022-03433-y/MediaObjects/11274_2022_3433_Fig3_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11274-022-03433-y/MediaObjects/11274_2022_3433_Fig4_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11274-022-03433-y/MediaObjects/11274_2022_3433_Fig5_HTML.png)
Similar content being viewed by others
Data availability
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
References
Alam K, Hao J, Zhang Y, Li A (2021a) Synthetic biology-inspired strategies and tools for engineering of microbial natural product biosynthetic pathways. Biotechnol Adv 49:107759
Alam K, Islam M, Li C, Sultana S, Zhong L, Shen Q et al (2021b) Genome mining of Pseudomonas species: diversity and evolution of metabolic and biosynthetic potential. Molecules 26:7524
Alam K, Hao J, Zhong L, Fan G, Ouyang Q, Islam M et al (2022a) Complete genome sequencing and in-silico genome mining reveals the promising metabolic potential in Streptomyces strain CS-7. Front Microbiol. https://doi.org/10.3389/fmicb.2022.939919
Alam K, Islam MM, Gong K, Abbasi MN, Li R, Zhang Y et al (2022b) In silico genome mining of potential novel biosynthetic gene clusters for drug discovery from Burkholderia bacteria. Comput Biol Med 140:105046
Alam K, Mazumder A, Sikdar S, Zhao YM, Hao J, Song C, Wang Y, Sarkar R, Islam S, Zhang Y, Li A (2022c) Streptomyces: the biofactory of secondary metabolites. Front Microbiol 13:968053
Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G et al (2013) Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep 30:108–160
Arocha-Garza HF, Canales-Del Castillo R, Eguiarte LE, Souza V, De la Torre-Zavala S (2017) High diversity and suggested endemicity of culturable Actinobacteria in an extremely oligotrophic desert oasis. Peer J 5:e3247
Aryal S, Neupane L, Adhikari R, Regmi B, Koirala N, Joshi DR (2021) Novel Streptomyces Sp. reported in 2018: a meta-analysis. Anti-Infect Agents 19(5):2–13
Augustine N, Kerkar S, Thomas S (2012) Arctic actinomycetes as potential inhibitors of Vibrio cholerae biofilm. Curr Microbiol 64:338–342
Babicki S, Arndt D, Marcu A, Liang Y, Grant JR, Maciejewski A et al (2016) Heatmapper: web-enabled heat mapping for all. Nucleic Acids Res 44:W147–W153
Belknap KC, Park CJ, Barth BM, Andam CP (2020) Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria. Sci Rep 10:1–9
Blin K, Shaw S, Kloosterman AM, Charlop-Powers Z, van Wezel GP, Medema MH et al (2021) antiSMASH 6.0: improving cluster detection and comparison capabilities. Nucleic Acids Res. https://doi.org/10.1093/nar/gkab335
Butler MS, Blaskovich MAT, Cooper MA (2017) Antibiotics in the clinical pipeline at the end of 2015. J Antibiot (Tokyo) 70:3–24. doi:https://doi.org/10.1038/ja.2016.72
Cao L, Do T, Link AJ (2021) Mechanisms of action of ribosomally synthesized and posttranslationally modified peptides (RiPPs). J Ind Microbiol Biotechnol 48:kuab005
Carroll CS, Moore MM (2018) Ironing out siderophore biosynthesis: a review of non-ribosomal peptide synthetase (NRPS)-independent siderophore synthetases. Crit Rev Biochem Mol Biol 53:356–381
Cimermancic P, Medema MH, Claesen J, Kurita K, Brown LCW, Mavrommatis K et al (2010) Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. Cell 158:412–421. https://doi.org/10.1016/j.cell.2014.06.034
Doroghazi JR, Albright JC, Goering AW, Ju K-S, Haines RR, Tchalukov KA et al (2014) A roadmap for natural product discovery based on large-scale genomics and metabolomics. Nat Chem Biol 10:963–968
Eddy SR (1998) Profile hidden Markov models. Bioinformatics 14:755–763
Encheva-Malinova M, Stoyanova M, Avramova H, Pavlova Y, Gocheva B, Ivanova I et al (2014) Antibacterial potential of streptomycete strains from Antarctic soils. Biotechnol Biotechnol Equip 28:721–727
Eto D, Watanabe K, Saeki H, Oinuma K, Otani K, Nobukuni M et al (2013) Divergent effects of desferrioxamine on bacterial growth and characteristics. J Antibiot (Tokyo) 66:199–203
Fischbach MA, Walsh CT, Clardy J (2008) The evolution of gene collectives: how natural selection drives chemical innovation. Proc Natl Acad Sci 105:4601–4608
Gallagher KA, Jensen PR (2015) Genomic insights into the evolution of hybrid isoprenoid biosynthetic gene clusters in the MAR4 marine streptomycete clade. BMC Genom 16:1–13
Jenke-Kodama H, Sandmann A, Müller R, Dittmann E (2005) Evolutionary implications of bacterial polyketide synthases. Mol Biol Evol 22:2027–2039
Katz L, Baltz RH (2016) Natural product discovery: past, present, and future. J Ind Microbiol Biotechnol 43:155–176
Kautsar SA, Blin K, Shaw S, Navarro-Muñoz JC, Terlouw BR, van der Hooft JJJ et al (2020) MIBiG 2.0: a repository for biosynthetic gene clusters of known function. Nucleic Acids Res 48:D454–D458
Kemung HM, Tan LT-H, Khan TM, Chan K-G, Pusparajah P, Goh B-H et al (2018) Streptomyces as a prominent resource of future anti-MRSA drugs. Front Microbiol 9:2221
Khadayat K, Sherpa DD, Malla KP, Shrestha S, Rana N, Marasini BP et al (2020) Molecular identification and antimicrobial potential of Streptomyces species from Nepalese soil. Int J Microbiol. https://doi.org/10.1155/2020/8817467
Khaldi N, Collemare J, Lebrun M-H, Wolfe KH (2008) Evidence for horizontal transfer of a secondary metabolite gene cluster between fungi. Genome Biol 9:1–10
Kroken S, Glass NL, Taylor JW, Yoder OC, Turgeon BG (2003) Phylogenomic analysis of type I polyketide synthase genes in pathogenic and saprobic ascomycetes. Proc Natl Acad Sci 100:15670–15675
Kumar S, Stecher G, Li M, Knyaz C, Tamura K (2018) MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 35:1547
Laskaris P, Tolba S, Calvo-Bado L, Wellington L (2010) Coevolution of antibiotic production and counter‐resistance in soil bacteria. Environ Microbiol 12:783–796
Lee N, Hwang S, Kim J, Cho S, Palsson B, Cho B-K (2020) Mini review: genome mining approaches for the identification of secondary metabolite biosynthetic gene clusters in Streptomyces. Comput Struct Biotechnol J 18:1548–1556
Li C, Alam K, Zhao Y, Hao J, Yang Q, Zhang Y et al (2021) Mining and biosynthesis of bioactive lanthipeptides from microorganisms. Front Bioeng Biotechnol. https://doi.org/10.3389/fbioe.2021.692466
Liu R, Deng Z, Liu T (2018) Streptomyces species: ideal chassis for natural product discovery and overproduction. Metab Eng 50:74–84
Medema MH, Cimermancic P, Sali A, Takano E, Fischbach MA (2014) A systematic computational analysis of biosynthetic gene cluster evolution: lessons for engineering biosynthesis. PLoS Comput Biol 10:e1004016
Mistry J, Chuguransky S, Williams L, Qureshi M, Salazar GA, Sonnhammer ELL et al (2021) Pfam: the protein families database in 2021. Nucleic Acids Res 49:D412–D419
Navarro-Muñoz JC, Selem-Mojica N, Mullowney MW, Kautsar SA, Tryon JH, Parkinson EI et al (2020) A computational framework to explore large-scale biosynthetic diversity. Nat Chem Biol 16:60–68. doi:https://doi.org/10.1038/s41589-019-0400-9
Newman DJ, Cragg GM (2020) Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod 83:770–803
Nicault M, Tidjani A-R, Gauthier A, Dumarcay S, Gelhaye É, Bontemps C et al (2020) Mining the biosynthetic potential for specialized metabolism of a Streptomyces soil community. Antibiotics 9:271
Niu G (2018) Genomics-driven natural product discovery in actinomycetes. Trends Biotechnol 36:238–241
Osbourn A (2010) Secondary metabolic gene clusters: evolutionary toolkits for chemical innovation. Trends Genet 26:449–457
Pham JV, Yilma MA, Feliz A, Majid MT, Maffetone N, Walker JR et al (2019) A review of the microbial production of bioactive natural products and biologics. Front Microbiol 10:1404
Ren H, Shi C, Zhao H (2020) Computational tools for discovering and engineering natural product biosynthetic pathways. Iscience 23:100795
Sarmiento-Vizcaíno A, González V, Braña AF, Palacios JJ, Otero L, Fernández J et al (2017) Pharmacological potential of phylogenetically diverse Actinobacteria isolated from deep-sea coral ecosystems of the submarine Avilés Canyon in the Cantabrian Sea. Microb Ecol 73:338–352
Scherlach K, Hertweck C (2009) Triggering cryptic natural product biosynthesis in microorganisms. Org Biomol Chem 7:1753–1760
Seipke RF, Kaltenpoth M, Hutchings MI (2012) Streptomyces as symbionts: an emerging and widespread theme? FEMS Microbiol Rev 36:862–876
Ser H-L, Tan LT-H, Law JW-F, Chan K-G, Duangjai A, Saokaew S et al (2017) Focused review: cytotoxic and antioxidant potentials of mangrove-derived Streptomyces. Front Microbiol 8:2065
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504
Skinnider MA, Johnston CW, Gunabalasingam M, Merwin NJ, Kieliszek AM, MacLellan RJ et al (2020) Comprehensive prediction of secondary metabolite structure and biological activity from microbial genome sequences. Nat Commun 11:1–9. doi:https://doi.org/10.1038/s41467-020-19986-1
Swayambhu G, Bruno M, Gulick AM, Pfeifer BA (2021) Siderophore natural products as pharmaceutical agents. Curr Opin Biotechnol 69:242–251
Tavaré S (1986) Some probabilistic and statistical problems in the analysis of DNA sequences. Lect Math life Sci 17:57–86
van Heel AJ, de Jong A, Song C, Viel JH, Kok J, Kuipers OP (2018) BAGEL4: a user-friendly web server to thoroughly mine RiPPs and bacteriocins. Nucleic Acids Res 46:W278–W281
Vurukonda SSKP, Giovanardi D, Stefani E (2018) Plant growth promoting and biocontrol activity of Streptomyces spp. as endophytes. Int J Mol Sci 19:952
Waksman SA (1953) Streptomycin: background, isolation, properties, and utilization. Science 118:259–266
Yoon S-H, Ha S-M, Lim J, Kwon S, Chun J (2017) A large-scale evaluation of algorithms to calculate average nucleotide identity. Antonie Van Leeuwenhoek 110:1281–1286
Zhao F, Qin Y-H, Zheng X, Zhao H-W, Chai D-Y, Li W et al (2016) Biogeography and adaptive evolution of Streptomyces strains from saline environments. Sci Rep 6:1–9
Ziemert N, Podell S, Penn K, Badger JH, Allen E, Jensen PR (2012) The natural product domain seeker NaPDoS: a phylogeny based bioinformatic tool to classify secondary metabolite gene diversity. PLoS ONE 7:1–9. https://doi.org/10.1371/journal.pone.0034064
Ziemert N, Lechner A, Wietz M, Millán-Aguiñaga N, Chavarria KL, Jensen PR (2014) Diversity and evolution of secondary metabolism in the marine actinomycete genus Salinispora. Proc Natl Acad Sci 111:E1130–E1139
Ziemert N, Alanjary M, Weber T (2016) The evolution of genome mining in microbes–a review. Nat Prod Rep 33:988–1005
Zotchev SB (2014) Genomics-based insights into the evolution of secondary metabolite biosynthesis in actinomycete bacteria. In: Evolutionary biology: genome evolution, speciation, coevolution and origin of life. Springer, Cham, pp 35–45
Funding
This study was supported by the National Key R&D Program of China (2018YFA0900400 and 2019YFA0905700), National Natural Science Foundation of China (32270088 and 32170038), the Open Project Program of the State Key Laboratory of Bio-based Material and Green Papermaking (KF201825) and the 111 Project (B16030).
Author information
Authors and Affiliations
Contributions
AL conceived the concept and funds, supervised the work, and validated the results. KA conducted all experiments, analyzed the data, and wrote the original draft of manuscript. KA, MMI, SI conducted software, JH, MNA, MH conducted validation, MS conducted formal analysis, YZ visualization and writing and data analysis. All authors read and approved the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflicts of interest to declare.
Consent for publication
Not applicable.
Consent to participate
Not applicable.
Ethical approval
Not applicable.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Alam, K., Islam, M.M., Islam, S. et al. Comparative genomics with evolutionary lineage in Streptomyces bacteria reveals high biosynthetic potentials. World J Microbiol Biotechnol 39, 64 (2023). https://doi.org/10.1007/s11274-022-03433-y
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11274-022-03433-y