Abstract
Streptomyces sp. KCTC 0041BP, which was isolated from a soil sample in Cheolwon, Republic of Korea, is a dihydrochalcomycin producer. In this study, we obtained the genome of S. sp. KCTC 0041BP with 7.54 Mb genome size. antiSMASH and the dbCAN2 meta server predicted that the genome would contain 26 secondary metabolite biosynthetic gene clusters (BGCs) and 285 carbohydrate-active enzymes. Besides dihydrochalcomycin, 21 compounds were successfully identified from S. sp. KCTC 0041BP, and among them, the structure of 8 compounds were proven by high-resolution electrospray ionization mass spectrometry (HRESIMS) and nuclear magnetic resonance (NMR). The identification of chalcomycin analogs led to a better understanding of the biosynthetic pathway of dihydrochalcomycin/chalcomycin. From the analysis of cluster 2 and solvent selection, linearmycins were determined. Linearmycins showed antibacterial activity with both Gram-positive and Gram-negative bacteria and antifungal activity. One strain many compounds (OSMAC) strategy was applied to activate the salicylic acid production in this strain. A salicylic acid biosynthetic pathway was also predicted, but not by antiSMASH. These results showed that this strain can produce many useful compounds and potentially produce novel compounds with most secondary BGCs yet to be experimentally identified.
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Asolkar RN, Maskey RP, Helmke E, Laatsch H (2002) Chalcomycin B, a new macrolide antibiotic from the marine isolate Streptomyces sp. B7064. J Antibiot (Tokyo) 55:893–898. https://doi.org/10.7164/antibiotics.55.893
Barger SR, Hoefler BC, Cubillos-Ruiz A, Russell WK, Russell DH, Straight PD (2012) Imaging secondary metabolism of Streptomyces sp. Mg1 during cellular lysis and colony degradation of competing Bacillus subtilis. Antonie van Leeuwenhoek. Int J Gen Mol Microbiol 102:435–445. https://doi.org/10.1007/s10482-012-9769-0
Barona-Gómez F, Wong U, Giannakopulos AE, Derrick PJ, Challis GL (2004) Identification of a cluster of genes that directs desferrioxamine biosynthesis in Streptomyces coelicolor M145. J Am Chem Soc 126:16282–16283. https://doi.org/10.1021/ja045774k
Bentley SD, Chater KF, Cerdeño-Tárraga AM, Challis GL, Thomson NR, James KD, Harris DE, Quail MA, Kieser H, Harper D, Bateman A, Brown S, Chandra G, Chen CW, Collins M, Cronin A, Fraser A, Goble A, Hidalgo J, Hornsby T, Howarth S, Huang CH, Kieser T, Larke L, Murphy L, Oliver K, O’Neil S, Rabbinowitsch E, Rajandream MA, Rutherford K, Rutter S, Seeger K, Saunders D, Sharp S, Squares R, Squares S, Taylor K, Warren T, Wietzorrek A, Woodward J, Barrell BG, Parkhill J, Hopwood DA (2002) Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417:141–147. https://doi.org/10.1038/417141a
Blin K, Shaw S, Steinke K, Villebro R, Ziemert N, Lee SY, Medema MH, Weber T (2019) AntiSMASH 5.0: updates to the secondary metabolite genome mining pipeline. Nucleic Acids Res 47:W81–W87. https://doi.org/10.1093/nar/gkz310
Chater KF (2016) Recent advances in understanding Streptomyces [version 1; referees: 4 approved]. F1000Research 5:1–16. https://doi.org/10.12688/f1000research.9534.1
Chernysheva N, Bystriskaya E, Stenkova A, Golovkin I, Nedashkovskaya O, Isaeva M (2019) Comparative genomics and CAZyme genome repertoires of marine Zobellia amurskyensis KMM 3526T and Zobellia laminariae KMM 3676T. Mar Drugs 17:661. https://doi.org/10.3390/md17120661
Chung YS, Kim DH, Seo WM, Lee HC, Liou K, Oh TJ, Sohng JK (2007) Enzymatic synthesis of dTDP-4-amino-4,6-dideoxy-d-glucose using GerB (dTDP-4-keto-6-deoxy-D-glucose aminotransferase). Carbohydr Res 342:1412–1418. https://doi.org/10.1016/j.carres.2007.04.007
Coffey GL, Anderson LE, Douros JD, Erlandson AL, Fisher MW, Hans RJ, Pittillo RF, Vogler DK, Weston KS, Ehrlich J (1963) Chalcomycin, a new antibiotic: biological studies. Can J Microbiol 9:665–669. https://doi.org/10.1139/m63-088
Dalisay DS, Williams DE, Wang XL, Centko R, Chen J, Andersen RJ (2013) Marine sediment-derived Streptomyces bacteria from British Columbia, Canada are a promising microbiota resource for the discovery of antimicrobial natural products. PLoS One 8:1–14. https://doi.org/10.1371/journal.pone.0077078
Dempsey DA, Vlot AC, Wildermuth MC, Klessig DF (2011) Salicylic acid biosynthesis and metabolism. In: The Arabidopsis Book. e0156. https://doi.org/10.1199/tab.0156
Genilloud O (2014) The re-emerging role of microbial natural products in antibiotic discovery. Antonie Van Leeuwenhoek 106:173–188. https://doi.org/10.1007/s10482-014-0204-6
Gomez-Escribano JP, Alt S, Bibb MJ (2016) Next generation sequencing of actinobacteria for the discovery of novel natural products. Mar Drugs 14:78. https://doi.org/10.3390/md14040078
Han J, Zhang J, Song Z, Zhu G, Liu M, Dai H, Hsiang T, Liu X, Zhang L, Quinn RJ, Feng Y (2020) Genome-based mining of new antimicrobial meroterpenoids from the phytopathogenic fungus Bipolaris sorokiniana strain 11134. Appl Microbiol Biotechnol 104:3835–3846. https://doi.org/10.1007/s00253-020-10522-1
Hodgson DA (2000) Primary metabolism and its control in Streptomycetes: a most unusual group of bacteria. Adv Microb Physiol 42:47–238. https://doi.org/10.1016/s0065-2911(00)42003-5
Hoefler BC, Stubbendieck RM, Josyula NK, Moisan SM, Schulze EM, Straight PD (2017) A link between linearmycin biosynthesis and extracellular vesicle genesis connects specialized metabolism and bacterial membrane physiology. Cell Chem Biol 24:1238–1249.e7. https://doi.org/10.1016/j.chembiol.2017.08.008
Huerta-Cepas J, Szklarczyk D, Forslund K, Cook H, Heller D, Walter MC, Rattei T, Mende DR, Sunagawa S, Kuhn M, Jensen LJ, von Mering C, Bork P (2016) eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences. Nucleic Acids Res 44:D286–D293. https://doi.org/10.1093/nar/gkv1248
Jaishy BP, Lim SK, Yoo ID, Yoo JC, Sohng JK, Nam DH (2006) Cloning and characterization of a gene cluster for the production of polyketide macrolide dihydrochalcomycin in Streptomyces sp. KCTC 0041BP. J Microbiol Biotechnol 16:764–770
Jiang S, Zhang L, Pei X, Deng F, Hu D, Chen G, Wang C, Hong K, Yao X, Gao H (2017) Chalcomycins from marine-derived Streptomyces sp. and their antimicrobial activities. Mar Drugs 15:153. https://doi.org/10.3390/md15060153
Katz L, Baltz RH (2016) Natural product discovery: past, present, and future. J Ind Microbiol Biotechnol 43:155–176. https://doi.org/10.1007/s10295-015-1723-5
Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA (2000) Practical Streptomyces genetics: a laboratory manual
Kim S-D, Ryoo I-J, Kim C-J, Kim W-G, Kim J-P, Kong J-Y, Koshino H, Uramoto M, Yoo I-D (1996) Geri-155, a new macrolide antibiotic related to chalcomycin. J Antibiot (Tokyo) 49:955–957. https://doi.org/10.7164/antibiotics.49.955
Koren S, Wallenz BP, Berlin K, Miller JR, Bergman NH, Phillippy AM (2017) Canu: scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation. Genome Res 27:722–736. https://doi.org/10.1101/gr.215087.116
Lagesen K, Hallin P, Rødland EA, Stærfeldt HH, Rognes T, Ussery DW (2007) RNAmmer: consistent and rapid annotation of ribosomal RNA genes. Nucleic Acids Res 35:3100–3108. https://doi.org/10.1093/nar/gkm160
Lee H-C, Sohng J-K, Kim H-J, Nam D-H, Han J-M, Cho S, Choi J-H, Yoo J-C (2004) Cloning and expression of the glucose-1-phosphate thymidylyltransferase gene (gerD) from Streptomyces sp. GERI-155. Mol Cell 17:274–280
Lefort V, Desper R, Gascuel O (2015) FastME 2.0: a comprehensive, accurate, and fast distance-based phylogeny inference program. Mol Biol Evol 32:2798–2800. https://doi.org/10.1093/molbev/msv150
Liu W, Nonaka K, Nie L, Zhang J, Christenson SD, Bae J, Van Lanen SG, Zazopoulos E, Farnet CM, Yang CF, Shen B (2005) The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases. Chem Biol 12:293–302. https://doi.org/10.1016/j.chembiol.2004.12.013
Lombard V, Golaconda Ramulu H, Drula E, Coutinho PM, Henrissat B (2014) The carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res 42:490–495. https://doi.org/10.1093/nar/gkt1178
Madeira F, Park YM, Lee J, Buso N, Gur T, Madhusoodanan N, Basutkar P, Tivey ARN, Potter SC, Finn RD, Lopez R (2019) The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic Acids Res 47:W636–W640. https://doi.org/10.1093/nar/gkz268
Malla S, Thuy TTT, Oh TJ, Sohng JK (2011) Identification and characterization of gerPI and gerPII involved in epoxidation and hydroxylation of dihydrochalcolactone in Streptomyces species KCTC 0041BP. Arch Microbiol 193:95–103. https://doi.org/10.1007/s00203-010-0648-7
Meier-Kolthoff JP, Auch AF, Klenk HP, Göker M (2013) Genome sequence-based species delimitation with confidence intervals and improved distance functions. BMC Bioinformatics 14:60. https://doi.org/10.1186/1471-2105-14-60
National Center for Biotechnology Information. (2021a) Genome, Streptomyces. https://www.ncbi.nlm.nih.gov/genome/13511. Accessed 7 Mar 2021
National Center for Biotechnology Information. (2021b) PubChem Compound Summary for CID 338, Salicylic acid. https://pubchem.ncbi.nlm.nih.gov/compound/Salicylic-acid. Accessed 2 Mar 2021b
Nett M, Ikeda H, Moore BS (2009) Genomic basis for natural product biosynthetic diversity in the actinomycetes. Nat Prod Rep 26:1362–1384. https://doi.org/10.1039/b817069j
Nguyen CT, Dhakal D, Pham VTT, Nguyen HT, Sohng JK (2020) Recent advances in strategies for activation and discovery/characterization of cryptic biosynthetic gene clusters in Streptomyces. Microorganisms 8:616. https://doi.org/10.3390/microorganisms8040616
Nouioui I, Carro L, García-López M, Meier-Kolthoff JP, Woyke T, Kyrpides NC, Pukall R, Klenk HP, Goodfellow M, Göker M (2018) Genome-based taxonomic classification of the phylum Actinobacteria. Front Microbiol 9:1–119. https://doi.org/10.3389/fmicb.2018.02007
Nybo SE, Shepherd MD, Bosserman MA, Rohr J (2010) Genetic manipulation of Streptomyces species. Curr Protoc Microbiol 19:1–26. https://doi.org/10.1002/9780471729259.mc10e03s19
Oki T, Konishi M, Tomatsu K, Tomita K, Saitoh KI, Tsunakawa M, Nishio M, Miyaki T, Kawaguchi H (1988) Pradimicin, a novel class of potent antifungal antibiotics. J Antibiot (Tokyo) 41:1701–1704. https://doi.org/10.7164/antibiotics.41.1701
Olanrewaju OS, Babalola OO (2019) Streptomyces: implications and interactions in plant growth promotion. Appl Microbiol Biotechnol 103:1179–1188. https://doi.org/10.1007/s00253-018-09577-y
Omura S, Ikeda H, Ishikawa J, Hanamoto A, Takahashi C, Shinose M, Takahashi Y, Horikawa H, Nakazawa H, Osonoe T, Kikuchi H, Shiba T, Sakaki Y, Hattori M (2001) Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites. Proc Natl Acad Sci U S A 98:12215–12220. https://doi.org/10.1073/pnas.211433198
Pageni BB, Oh TJ, Thuy TTT, Sohng JK (2008) Characterization of a chalcosyltransferase (gerGTII) in dihydrochalcomycin biosynthesis. Mol Cell 26:278–284
Pageni BB, Oh TJ, Sohng JK (2009) Novel desosaminyl derivatives of dihydrochalcomycin from a genetically engineered strain of Streptomyces sp. Biotechnol Lett 31:1759–1768. https://doi.org/10.1007/s10529-009-0074-6
Pageni BB, Simkhada D, Oh TJ, Sohng JK (2010) Biosynthesis of dihydrochalcomycin: characterization of a deoxyallosyltransferase (gerGTI). Mol Cell 29:153–158. https://doi.org/10.1007/s10059-010-0019-x
Pan G, Xu Z, Guo Z, Hindra MM, Yang D, Zhou H, Gansemans Y, Zhu X, Huang Y, Zhao L-X, Jiang Y, Cheng J, Van Nieuwerburgh F, Suh J-W, Duan Y, Shen B (2017) Discovery of the leinamycin family of natural products by mining actinobacterial genomes. Proc Natl Acad Sci U S A 114:E11131–E11140. https://doi.org/10.1073/pnas.1716245115
Pham VTT, Nguyen HT, Nguyen CT, Choi YS, Dhakal D, Kim TS, Jung HJ, Yamaguchi T, Sohng JK (2021) Identification and enhancing production of a novel macrolide compound in engineered: Streptomyces peucetius. RSC Adv 11:3168–3173. https://doi.org/10.1039/d0ra06099b
Qi Q-Y, Huang L, He L-W, Han J-J, Chen Q, Cai L, Liu H-W (2014) Cochlioquinone derivatives with apoptosis-inducing effects on HCT116 colon cancer cells from the phytopathogenic fungus Bipolaris luttrellii L439. Chem Biodivers 11:1892–1899. https://doi.org/10.1002/cbdv.201400106
Rodriguez-R LM, Konstantinidis KT (2016) The enveomics collection: a toolbox for specialized analyses of microbial genomes and metagenomes. PeerJ Prepr. https://doi.org/10.7287/peerj.preprints.1900v1
Sakuda S, Guce-Bigol U, Itoh M, Nishimura T, Yamada Y (1995) Linearmycin A, a novel linear polyene antibiotic. Tetrahedron Lett 36:2777–2780. https://doi.org/10.1016/0040-4039(95)00392-P
Schattner P, Brooks AN, Lowe TM (2005) The tRNAscan-SE, snoscan and snoGPS web servers for the detection of tRNAs and snoRNAs. Nucleic Acids Res 33:686–689. https://doi.org/10.1093/nar/gki366
Schmerk CL, Welander PV, Hamad MA, Bain KL, Bernards MA, Summons RE, Valvano MA (2015) Elucidation of the Burkholderia cenocepacia hopanoid biosynthesis pathway uncovers functions for conserved proteins in hopanoid-producing bacteria. Environ Microbiol 17:735–750. https://doi.org/10.1111/1462-2920.12509
Seemann T (2014) Prokka: rapid prokaryotic genome annotation. Bioinformatics 30:2068–2069. https://doi.org/10.1093/bioinformatics/btu153
Sproule AT (2016) Discovery of cryptic microbial natural products using induction strategies and characterization of a novel biotransformation product. University of Prince Edward Island
Stroeve P, Pettit CD, Vasquez V, Kim I, Berry AM (1998) Surface active behavior of hopanoid lipids: bacteriohopanetetrol and phenylacetate monoester bacteriohopanetetrol. Langmuir 14:4261–4265. https://doi.org/10.1021/la980013e
Su C, Yan Y, Guo X, Luo J, Liu C, Zhang Z, Xiang W-S, Huang S-X (2019) Characterization of the N-methyltransferases involved in the biosynthesis of toxoflavin, fervenulin and reumycin from Streptomyces hiroshimensis ATCC53615. Org Biomol Chem 17:477–481. https://doi.org/10.1039/c8ob02847h
The CAZypedia Consortium (2018) Ten years of CAZypedia: a living encyclopedia of carbohydrate-active enzymes. Glycobiology 28:3–8. https://doi.org/10.1093/glycob/cwx089
Thibodeaux CJ, Melançon CE, Liu H-W (2008) Natural product sugar biosynthesis and enzymatic glycodiversification. Angew Chem Int Ed 47:9814–9859. https://doi.org/10.1002/anie.200801204
Thuy TTT, Sohng JK, Pfeifer B (2010) Dihydrochalcomycin production and glycosyltransferase from Streptomyces sp. KCTC 0041BP. J Int Fed Clin Chem Lab Med 20:171–175
Ueda K, Oinuma K-I, Ikeda G, Hosono K, Ohnishi Y, Horinouchi S, Beppu T (2002) AmfS, an extracellular peptidic morphogen in Streptomyces griseus. J Bacteriol 184:1488–1492. https://doi.org/10.1128/JB.184.5.1488-1492.2002
Wang W-G, Du L-Q, Sheng S-L, Li A, Li Y-P, Cheng G-G, Li G-P, Sun G, Hu Q-F, Matsuda Y (2019) Genome mining for fungal polyketide-diterpenoid hybrids: discovery of key terpene cyclases and multifunctional P450s for structural diversification. Org Chem Front 6:571–578. https://doi.org/10.1039/c8qo01124a
Wang B, Guo F, Huang C, Zhao H (2020) Unraveling the iterative type I polyketide synthases hidden in Streptomyces. Proc Natl Acad Sci U S A 117:8449–8454. https://doi.org/10.1073/pnas.1917664117
Weber T, Laiple KJ, Pross EK, Textor A, Grond S, Welzel K, Pelzer S, Vente A, Wohlleben W (2008) Molecular analysis of the kirromycin biosynthetic gene cluster revealed β-alanine as precursor of the pyridone moiety. Chem Biol 15:175–188. https://doi.org/10.1016/j.chembiol.2007.12.009
Yoganathan K, Yang L-K, Rossant C, Huang Y, Ng S, Butler MS, Buss AD (2004) Cochlioquinones and Epi-cochlioquinones: antagonists of the human chemokine receptor CCR5 from Bipolaris brizae and Stachybotrys chartarum. J Antibiot (Tokyo) 57:59–63. https://doi.org/10.7164/antibiotics.57.59
Zhang H, Yohe T, Huang L, Entwistle S, Wu P, Yang Z, Busk PK, Xu Y, Yin Y (2018) dbCAN2: a meta server for automated carbohydrate-active enzyme annotation. Nucleic Acids Res 46:W95–W101. https://doi.org/10.1093/nar/gky418
Ziemert N, Alanjary M, Weber T (2016) The evolution of genome mining in microbes-a review. Nat Prod Rep 33:988–1005. https://doi.org/10.1039/c6np00025h
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This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MEST) (NRF-2021R1A2C2004775).
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Nguyen, C.T., Bridget, A.F., Pham, V.T.T. et al. Genome mining Streptomyces sp. KCTC 0041BP as a producer of dihydrochalcomycin. Appl Microbiol Biotechnol 105, 5023–5037 (2021). https://doi.org/10.1007/s00253-021-11393-w
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DOI: https://doi.org/10.1007/s00253-021-11393-w