Precursor-directed combinatorial biosynthesis of cephalosporin analogue by endolithic actinobacterium Streptomyces sp. AL51 by utilizing thiophene derivative
Natural products or their derivatives provide a reliable resource for new drugs. The multi-step chemical reaction to produce new drug is not only expensive but also release pollutants. The precursor-based combinatorial biosynthesis (PCB) is, however, a better option to produce novel natural products with potential pharmaceutical applications. The present work is an attempt to synthesize an antibacterial compound by transforming thiophene precursor using endolithic Streptomyces sp. AL51. The Streptomyces sp. AL51 was isolated from a granite rock sample collected from Mylliem, Meghalaya, India. The isolate was identified as Streptomyces sp. based on its cultural, morphological, biochemical and molecular characteristics. The bioactive compound CAx1 was extracted from the fermentation broth. The compound was characterized by bioactivity-guided fractionation and identified by infrared, UV–visible, nuclear magnetic resonance and mass spectrometry data and identified as 7-[1-(thiophene-5-yl)-1-formamido]-3-propylenyl-3-cephem-4-carboxylic acid with molecular formula C15H14N2O4S2. The purified compound showed considerable in vitro antibacterial activity against both Gram-positive and Gram-negative bacteria showing its broad spectrum property. The obtained results provide promising baseline information for the potential use of endolithic actinobacterium for semisynthetic drug discovery. This is the first report on PCB of broad range antibacterial compound by endolithic Streptomyces strain.
KeywordsEndolithic Streptomyces Cephalosporin analogue Precursor based combinatorial biosynthesis Antibacterial
The NMR facility was provided by S.A.I.F, N.E.H.U, Shillong. The UV–Visible spectroscopic facility was provided by Central Instrumentation Facility, School of Life Sciences, N.E.H.U, Shillong and FT-IR facility was provided by C.I.F, I.A.S.S.T, Guwahati. We are also grateful to Dr. S. Sangilipandi, Centre for Advanced Studies in Chemistry, N.E.H.U, Shillong for the help during TLC and purification studies. Authors acknowledge the partial financial support by the DST-FIST programme of Department of Science & Technology, Government of India for the research.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
Research involving human and animal participants
This article does not contain any studies with human participants or animals performed by any of the authors.
- Alexander DC, Jensen SE (1998) Investigation of the Streptomyces clavuligerus cephamycin C gene cluster and its regulation by the CcaR protein. J Bacteriol 180(16):4068–4079Google Scholar
- Bhattacharjee K, Banerjee S, Bawitlung L, Krishnappa D, Joshi SR (2014) A study on parameters optimization for degradation of endosulfan by bacterial consortia isolated from contaminated soil. Proc Natl Acad Sci India Sect B Biol Sci 84(3):657–667. https://doi.org/10.1007/s40011-013-0223-5 CrossRefGoogle Scholar
- Blicke FF (1952) Biological and pharmacological activity of thiophene and its derivatives. In: Hartough HD (ed) Chemistry of heterocyclic compounds: thiophene and its derivatives, vol 3. Interscience Publishers, New York, pp 29–45Google Scholar
- Coates J (2000) Interpretation of infrared spectra, a practical approach. In: Meyers RA (ed) Encyclopedia of analytical chemistry. John, Chichester, pp 1–22Google Scholar
- Coldham NG, Webber M, Woodward MJ, Piddock LJ (2010) A 96-well plate fluorescence assay for assessment of cellular permeability and active efflux in Salmonella enterica serovar Typhimurium and Escherichia coli. J Antimicrob Chemother 65(8):1655–1663. https://doi.org/10.1093/jac/dkq169 CrossRefGoogle Scholar
- Fajardo-Cavazos P, Nicholson W (2006) Bacillus endospores isolated from granite: close molecular relationships to globally distributed Bacillus spp. from endolithic and extreme environments. Appl Environ Microbiol 72(4):2856–2863. https://doi.org/10.1128/AEM.72.4.2856-2863.2006 CrossRefGoogle Scholar
- González A, Rodríguez M, Braña AF, Méndez C, Salas JA, Olano C (2016) New insights into paulomycin biosynthesis pathway in Streptomyces albus J1074 and generation of novel derivatives by combinatorial biosynthesis. Microb Cell Fact 15:56. https://doi.org/10.1186/s12934-016-0452-4 CrossRefGoogle Scholar
- Holt JG (1994) Bergey’s manual of determinative bacteriology, 9th edn. Lippincott Williams and Wilkins, BaltimoreGoogle Scholar
- Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA (2000) Practical Streptomyces Genetics. John Innes Foundation, Norwich, pp 44–47Google Scholar
- Palepu NR, Nongbri SL, Premkumar JR, Verma AK, Bhattacharjee K et al (2015) Synthesis and evaluation of new salicylaldehyde-2-picolinylhydrazone Schiff base compounds of Ru(II), Rh(III) and Ir(III) as in vitro antitumor, antibacterial and fluorescence imaging agents. J Biol Inorg Chem 20(4):619–638. https://doi.org/10.1007/s00775-015-1249-3 CrossRefGoogle Scholar
- Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4(4):406–425. https://doi.org/10.1093/oxfordjournals.molbev.a040454 Google Scholar
- Selvin J, Shanmughapriya S, Gandhimathi R, SeghalKiran G, RajeethaRavji T et al (2009) Optimization and production of novel antimicrobial agents from sponge associated marine actinomycetes Nocardiopsis dassonvillei MAD08. Appl Microbiol Biotechnol 83(3):435–445. https://doi.org/10.1007/s00253-009-1878-y CrossRefGoogle Scholar
- Sletta H, Degnes KF, Herfindal L, Klinkenberg G, Fjærvik E et al (2014) Anti-microbial and cytotoxic 1,6-dihydroxyphenazine-5,10-dioxide(iodinin) produced by Streptosporangium sp. DSM 45942 isolated from the fjord sediment. Appl Microbiol Biotechnol 98(2):603–610. https://doi.org/10.1007/s00253-013-5320-0 CrossRefGoogle Scholar
- Vaca I, Casqueiro J, Ullán RV, Rumbero A, Chávez R, Martín JF (2011) A preparative method for the purification of isopenicillin N from genetically blocked Acremonium chrysogenum strain TD189: studies on the degradation kinetics and storage conditions. J Antibiot (Tokyo) 64:447–451. https://doi.org/10.1038/ja.2011.30 CrossRefGoogle Scholar
- Wierzchos J, Camara B, de Los Rios A, Davila AF, Sanchez Almazo IM et al (2011) Microbial colonization of Ca-sulfate crusts in the hyperarid core of the Atacama Desert: implications for the search for life on Mars. Geobiology 9(1):44–60. https://doi.org/10.1111/j.1472-4669.2010.00254.x CrossRefGoogle Scholar