School of Biotechnology

Madurai Kamaraj University, Madurai

Dr. Ranjan Prasad
Reader
Department of Genetic Engineering
Telephone : 0452 2459115 (O)
               :0452 2458159 (R)
Fax : 0452-2459105
Email :ranjan_mku@yahoo.com


Current Research Programmes:

  1. Biochemical and genetic analysis of daunorubicin (DNR) binding proteins of Streptomyces peucetius.
  2. Self resistance of S. peucetius to DNR by efflux pumps such as the drrAB and others.
  3. Identification of non-biosynthetic genes important for anthracycline biosynthesis in S. peucetius.

Research

A novel secreted protein of Streptomyces peucetius was discovered that binds strongly daunorubicin that is exported by the organism (Ranjan Prasad et al 2003). In the first programme we have started the process of identifying DNR binding extracellular proteins using the MALDI-ToF analysis. Genes encoding the proteins will be cloned for expression. Disrupting the gene will show the function in connection with biosynthesis of the drug and self resistance in S. peucetius. Also In vitro drug-protein interaction kinetics will be investigated using the binding protein.

The second programme is on drrAB genes that encode for ATP dependent DNR efflux pump. Mechanism of action of this protein for drug efflux will be studied in detail. We have found that there is also another pump that could also efflux of DNR, which will be identified in due course of time. Eventually the regulation of these genes of the efflux pump in relation of DNR biosynthesis by the cell is to be investigated.

Third programme is to identify and characterize genes that are not directly involved in DNR biosynthesis but influence it indirectly. For this, S. peucetius will be mutagenised by a new and efficient transposon technique. In this way we plan to standardize genome-wide transposon mutagenesis of Streptomyces that is considerably refractory to transposon integration.

Publication

 

  1. Padmanabhan S., P. Naynar and R. Prasad (2010) Daunorubicin efflux in Streptomyces peucetius modulates biosynthesis by feed back regulation. FEMS Microbiol. Lett. (DOI:10.1111/j.1574-6968.2010. 01905.x).
  1. Ajith V.K. and R. Prasad (2010) The activator/repressor protein DnrO of Streptomyces peucetius binds to DNA without changing its topology. Int. J. Biol. Macromol. (In Press).
  1. Ajithkumar V and Ranjan Prasad (2009) A novel protein that binds to dnrN-dnrO intergenic region of Streptomyces peucetius purified by DNA affinity capture has dihydrolipoamide dehydrogenase activity Protein Expression and Purif. 67: 132-138.
  1. Ranjan Prasad, Sasikala, V., Vetrivel, K.S. and Dharmalingam, K. (2003) A novel extracellular protein of Streptomyces peucetius binds to daunorubicin but does not inhibit the bioactivity of the antibiotic. Biochem. Biophys. Res. Commun. 311: 460 – 464.
  1. Shivapriya R, Prasad R, Iyer Lakshminarayanan, Krishnaswamy S and Dharmalingam K (1995) Expression of mcrA gene of E.coli is regulated by sequestration of translational signal.  Gene. 157: 201-207.
  1. Ramalingam R, Ranjan Prasad, Shivapriya R. and Dharmalingam K (1992) Molecular Cloning and sequencing of mcrA locus and identification of McrA protein in Escherichia coli. J. Bio. Sci. 17:217-232.
  1. Sozhamannan S, Raja M C, Ranjan Prasad, Kamla Chaudhary, Shivakumar B and Dharmalingam K (1992) Molecular cloning of the mcrBC (rglB) locus of Escherichia coli K12 and identification of the mcrBC encoded proteins. Proc. Indian Natl. Sci. Acad. B58: 253-264

Ongoing Project:

Genetic and biochemical investigation of daunorubicin-binding protein in Streptomyces peucetius, funded by DBT, 2006-09

People

Research Scholars

  • S. Padmanabhan
  • K. Rashmi
  • K.Karuppasamy


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