Analyzing the biosynthetic potential of antimicrobial-producing actinobacteria originating from Indonesia
Anissa Utami(1), Pamela Apriliana(2), Yudi Kusnadi(3), Dewi S. Zilda(4), Zidny Ilmiah(5), Puspita Lisdiyanti(6), Siswa Setyahadi(7*), Agustinus R. Uria(8)
(1) Graduate School of Pharmacy, Pancasila University, Jl. Raya Lenteng Agung, Jakarta Selatan 12630, Indonesia; Politeknik Hang Tuah Jakarta, Jl. Bendungan Hilir Jakarta Pusat 10210, Indonesia
(2) Research Center for Biotechnology, Indonesian Institute of Sciences (LIPI), Jl. LIPI, Cibinong, Bogor, Jawa Barat 16911, Indonesia
(3) Research Center for Marine and Fisheries Product processing and Biotechnology Ministry of Marine Affairs and Fisheries, JL. KS Tubun Petamburan VI, Slipi, Jakarta Pusat 10260, Indonesia; Life Science Division, ITS Science Indonesia, Jl. Boulevard Artha Gading, Jakarta Utara 14240, Indonesia
(4) Research Center for Marine and Fisheries Product processing and Biotechnology Ministry of Marine Affairs and Fisheries, JL. KS Tubun Petamburan VI, Slipi, Jakarta Pusat 10260, Indonesia
(5) Research Center for Biotechnology, Indonesian Institute of Sciences (LIPI), Jl. LIPI, Cibinong, Bogor, Jawa Barat 16911, Indonesia
(6) Research Center for Biotechnology, Indonesian Institute of Sciences (LIPI), Jl. LIPI, Cibinong, Bogor, Jawa Barat 16911, Indonesia
(7) Graduate School of Pharmacy, Pancasila University, Jl. Raya Lenteng Agung, Jakarta Selatan 12630, Indonesia; Center of Bio-industrial Technology, Agency for Technology Assessment and Development, Tangerang Selatan, Banten 15314, Indonesia
(8) Research Center for Marine and Fisheries Product processing and Biotechnology Ministry of Marine Affairs and Fisheries, JL. KS Tubun Petamburan VI, Slipi, Jakarta Pusat 10260, Indonesia; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita Ward, Sapporo, Hokkaido 060-0812, Japan
(*) Corresponding Author
Abstract
We investigated the biosynthetic potential of soil-associated actinobacteria originating from Indonesia, identified as Streptomyces luridus and as Streptomyces luteosporeus. Antimicrobial assays indicated inhibitory activity by both strains against the pathogen Pseudomonas aeruginosa, with S. luteosporeus particularly inhibiting the growth of Bacillus subtilis. PCR-amplification, cloning, and sequencing of ketosynthase (KS) domains of type I modular polyketide (PKS-I) and adenylation (AD) domains of non-ribosomal peptide synthetase (NRPS) indicated the diversity of KS and AD domains derived from both Indonesian Streptomyces. Further phylogenetic analysis showed that KS domains from the subclass cis-AT PKS can be classified as being a part of a loading module or an extension module, along with their predicted substrate specificity. The results suggest that both strains are a potential source of novel biosynthetic pathways. This genetic analysis approach can be used as a fast guide to obtain insight into natural product biosynthetic gene diversity in microorganisms.
Keywords
Full Text:
PDFReferences
Aotani Y, Nagata H, Yoshida M. 1997. Lymphostin (LK6 A), a novel immunosuppressant from Streptomyces sp. KY11783: Structural elucidation. J Antibiot. 50(7):543–545. doi:10.7164/antibiotics.50.543.
Aparicio JF, Molnár I, Schwecke T, König A, Haydock SF, Khaw LE, Staunton J, Leadlay PF. 1996. Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: Analysis of the enzymatic domains in the modular polyketide synthase. Gene. 169(1):9–16. doi:10.1016/0378 1119(95)008004. A
yusoSacido A, Genilloud O. 2005. New PCR primers for the screening of NRPS and PKSI systems in actinomycetes: Detection and distribution of these biosynthetic gene sequences in major taxonomic groups. Microb Ecol. 49(1):10–24. doi:10.1007/s0024800402496.
Bérdy J. 2005. Bioactive microbial metabolites: A personal view. J Antibiot. 58(1):1–26. doi:10.1038/ja.2005.1.
Buntin K, Irschik H, Weissman KJ, Luxenburger E, Blöcker H, Müller R. 2010. Biosynthesis of Thuggacins in Myxobacteria: Comparative Cluster Analysis Reveals Basis for Natural Product Structural Diversity. Chem Biol. 17(4):342–356. doi:10.1016/j.chembiol.2010.02.013.
Cane DE, Walsh CT. 1999. The parallel and convergent universes of polyketide synthases and nonribosomal peptide synthetases. Chem Biol. 6(12). doi:10.1016/S10745521(00)800010.
Celmer WD, Solomons IA. 1955. The Structures of Thiolutin and Aureothricin, Antibiotics Containing a Unique Pyrrolinonodithiole Nucleus. J Am Chem. Soc. 77(10):2861–2865. doi:10.1021/ja01615a058.
Edgar RC. 2004. MUSCLE: Multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32(5):1792–1797. doi:10.1093/nar/gkh340.
Engl T, Kroiss J, Kai M, Nechitaylo TY, Svatoš A, Kaltenpoth M. 2018. Evolutionary stability of antibiotic protection in a defensive symbiosis. Proc Natl Acad Sci USA. 115(9):E2020–E2029. doi:10.1073/pnas.1719797115.
Fawzya YN, Zilda DS, Chaniago S, Prestisia HN, Lisdiyanti P, Khasanah N. 2016. Screening of Indonesian Streptomyces sp. capable of secreting transglutaminase (MTGase) and optimization of MTGase production using different growth media. Squalen Bulletin of Marine and Fisheries Postharvest and Biotechnology 11(1):13–21.
Fischbach MA, Walsh CT. 2006. Assemblyline enzymology for polyketide and nonribosomal peptide antibiotics: Logic machinery, and mechanisms. Chem Rev. 106(8):3468–3496. doi:10.1021/cr0503097.
Gerlt JA, Allen KN, Almo SC, Armstrong RN, Babbitt PC, Cronan JE, DunawayMariano D, Imker HJ, Jacobson MP, Minor W, et al. 2011. The enzyme function initiative. Biochemistry. 50(46):9950–9962. doi:10.1021/bi201312u.
Gerlt JA, Bouvier JT, Davidson DB, Imker HJ, Sadkhin B, Slater DR, Whalen KL. 2015. Enzyme function initiativeenzyme similarity tool (EFIEST): A web tool for generating protein sequence similarity networks. Biochim Biophys Acta, Proteins Proteomics. 1854(8):1019–1037. doi:10.1016/j.bbapap.2015.04.015.
Gunsior M, Breazeale SD, Lind AJ, Ravel J, Janc JW, Townsend CA. 2004. The biosynthetic gene cluster for a monocyclic βlactam antibiotic, nocardicin A. Chem Biol. 11(7):927–938. doi:10.1016/j.chembiol.2004.04.012.
Hertweck C. 2009. The biosynthetic logic of polyketide diversity. Angewandte Chemie International Edition 48(26):4688–4716. doi:10.1002/anie.200806121.
Hertweck C. 2015. Decoding and reprogramming complex polyketide assembly lines: Prospects for synthetic biology. Trends Biochem Sci. 40(4):189–199. doi:10.1016/j.tibs.2015.02.001.
Jokela J, Heinilä LM, Shishido TK, Wahlsten M, Fewer DP, Fiore MF, Wang H, Haapaniemi E, Permi P, Sivonen K. 2017. Production of high amounts of hepatotoxin nodularin and new protease inhibitors pseudospumigins by the brazilian benthic Nostoc sp. CENA543. Front Microbiol. 8(OCT). doi:10.3389/fmicb.2017.01963.
Jones DT, Taylor WR, Thornton JM. 1992. The rapid generation of mutation data matrices from protein sequences. Bioinformatics 8(3):275–282. doi:10.1093/bioinformatics/8.3.275.
Kautsar SA, Blin K, Shaw S, NavarroMuñoz JC, Terlouw BR, Van Der Hooft JJ, Van Santen JA, Tracanna V, Suarez Duran HG, Pascal Andreu V, et al. 2020. MIBiG 2.0: A repository for biosynthetic gene clusters of known function. Nucleic Acids Res. 48(D1):D454–D458. doi:10.1093/nar/gkz882.
Konz D, Marahiel MA. 1999. How do peptide synthetases generate structural diversity? Chem. Biol. 6(2). doi:10.1016/S10745521(99)800027.
Kumar S, Stecher G, Li M, Knyaz C, Tamura K. 2018. MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol Biol. Evol. 35(6):1547–1549. doi:10.1093/molbev/msy096.
Labeda DP, Goodfellow M, Brown R, Ward AC, Lanoot B, Vanncanneyt M, Swings J, Kim SB, Liu Z, Chun J, et al. 2012. Phylogenetic study of the species within the family Streptomycetaceae. In: Antonie Van Leeuwenhoek., volume 101. p. 73–104. doi:10.1007/s1048201196560.
Lamilla C, Braga D, Castro R, Guimarães C, de Castilho LV, Freire DM, Barrientos L. 2018. Streptomyces luridus So3.2 from Antarctic soil as a novel producer of compounds with bioemulsification potential. PLoS ONE. 13(4). doi:10.1371/journal.pone.0196054.
Liu C, Jiang Y, Wang X, Chen D, Chen X, Wang L, Han L,Huang X, Jiang C. 2017. Diversity, Antimicrobial Activity, and Biosynthetic Potential of Cultivable Actinomycetes Associated with Lichen Symbiosis. Microb Ecol. 74(3):570–584. doi:10.1007/s00248017 09724.
Liu Q, Yao F, Chooi YH, Kang Q, Xu W, Li Y, Shao Y, Shi Y, Deng Z, Tang Y, You D. 2012. Elucidation of piericidin A1 biosynthetic locus revealed a thioesterasedependent mechanism of α pyridone ring formation. Chem Biol. 19(2):243–253. doi:10.1016/j.chembiol.2011.12.018.
Miyanaga A. 2017. Structure and function of polyketide biosynthetic enzymes: various strategies for production of structurally diverse polyketides. doi:10.1080/09168451.2017.1391687.
Moradali MF, Ghods S, Rehm BH. 2017. Pseudomonas aeruginosa lifestyle: A paradigm for adaptation, survival, and persistence. Front Cell Infect Microbiol. 7(FEB). doi:10.3389/fcimb.2017.00039.
Morgulis A, Coulouris G, Raytselis Y, Madden TL, Agarwala R, Schäffer AA. 2008. Erratum: Database indexing for production MegaBLAST searches. Bioinformatics 24(24):2942. doi:10.1093/bioinformatics/btn554.
Murphy AC, Hong H, Vance S, Broadhurst RW, Leadlay PF. 2016. Broadening substrate specificity of a chainextending ketosynthase through a single activesite mutation. Chem Commun. 52(54):8373–8376. doi:10.1039/c6cc03501a.
Nguyen TA, Ishida K, JenkeKodama H, Dittmann E, Gurgui C, Hochmuth T, Taudien S, Platzer M, Hertweck C, Piel J. 2008. Exploiting the mosaic structure of transacyltransferase polyketide synthases for natural product discovery and pathway dissection. Nat Biotechnol. 26(2):225–233. doi:10.1038/nbt1379.
Nishizawa T, Asayama M, Fujii K, Harada KI, Shirai M. 1999. Genetic analysis of the peptide synthetase genes for a cyclic heptapeptide microcystin in Microcystis spp. J Biochem. 126(3):520–529. doi:10.1093/oxfordjournals.jbchem.a022481.
Piel J. 2002. A polyketide synthasepeptide synthetase gene cluster from an uncultured bacterial symbiont of Paederus beetles. Proc Natl Acad Sci USA. 99(22):14002–14007. doi:10.1073/pnas.222481399.
Piel J, Hui D, Wen G, Butzke D, Platzer M, Fusetani N, Matsunaga S. 2004. Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei. Proc Natl Acad Sci USA. 101(46):16222–16227. doi:10.1073/pnas.0405976101.
Rawlings BJ. 2001. Type I polyketide biosynthesis in bacteria (Part A Erythromycin biosynthesis). Nat Prod Rep. 18(2):190–227. doi:10.1039/b009329g.
Risdian C, Mozef T, Wink J. 2019. Biosynthesis of polyketides in Streptomyces. Microorganisms. 7(5). doi:10.3390/microorganisms7050124.
Robbins T, Kapilivsky J, Cane DE, Khosla C. 2016. Roles of Conserved Active Site Residues in the Ketosynthase Domain of an Assembly Line Polyketide Synthase. Biochemistry. 55(32):4476–4484. doi:10.1021/acs.biochem.6b00639.
Röttig M, Medema MH, Blin K, Weber T, Rausch C, Kohlbacher O. 2011. NRPSpredictor2 A web server for predicting NRPS adenylation domain specificity. Nucleic Acids Research 39(SUPPL. 2). doi:10.1093/nar/gkr323.
Saitou N, Nei M. 1987. The neighborjoining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 4(4):406–425. doi:10.1093/oxfordjournals.molbev.a040454.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. 2003. Cytoscape: A software Environment for integrated models of biomolecular interaction networks. Genome Res. 13(11):2498–2504. doi:10.1101/gr.1239303.
Shao L, Zi J, Zeng J, Zhan J. 2012. Identification of the herboxidiene biosynthetic gene cluster in Streptomyces chromofuscus ATCC 49982. Appl Environ. Microbiol. 78(6):2034–2038. doi:10.1128/AEM.0690411.
Sievers F, Higgins DG. 2018. Clustal Omega for making accurate alignments of many protein sequences. Protein Science 27(1):135–145. doi:10.1002/pro.3290.
Silakowski B, Schairer HU, Ehret H, Kunze B, Weinig S, Nordsiek G, Brandt P, Blöcker H, Höfle G, Beyer S, Müller R. 1999. New lessons for combinatorial biosynthesis from myxobacteria. The myxothiazol biosynthetic gene cluster of Stigmatella aurantiaca DW4/31. J Biol Chem. 274(52):37391–37399. doi:10.1074/jbc.274.52.37391.
Tillett D, Dittmann E, Erhard M, Von Döhren H, Börner T, Neilan BA. 2000. Structural organization of microcystin biosynthesis in Microcystis aeruginosa PCC7806: An integrated peptidepolyketide synthetase system. Chem Biol. 7(10):753–764. doi:10.1016/S10745521(00)000211.
van der Meij A, Worsley SF, Hutchings MI, van Wezel GP. 2017. Chemical ecology of antibiotic production by actinomycetes. doi:10.1093/femsre/fux005.
Watanabe K, Wang CC, Boddy CN, Cane DE, Khosla C. 2003. Understanding Substrate Specificity of Polyketide Synthase Modules by Generating Hybrid Multimodular Synthases. J Biol Chem. 278(43):42020– 42026. doi:10.1074/jbc.M305339200.
Weisburg WG, Barns SM, Pelletier DA, Lane DJ. 1991. 16S ribosomal DNA amplification for phylogenetic study. J Bacteriol. 173(2):697–703. doi:10.1128/jb.173.2.697703.1991.
Weissman KJ. 2015. Uncovering the structures of modular polyketide synthases. Natural Product Reports 32(3):436–453. doi:10.1039/c4np00098f.
Xue Y, Zhao L, Liu HW, Sherman DH. 1998. A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: Architecture of metabolic diversity. Proc Natl Acad Sci US. A. 95(21):12111–12116.doi:10.1073/pnas.95.21.12111.
Yang CC, Iwasaki W. 2014. MetaMetaDB: A database and analytic system for investigating microbial habitability. PLoS ONE. 9(1). doi:10.1371/journal.pone.0087126.
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(3). doi:10.1371/journal.pone.0034064.
DOI: https://doi.org/10.22146/ijbiotech.65239
Article Metrics
Abstract views : 2526 | views : 2572Refbacks
- There are currently no refbacks.
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.