Steps towards an Arthrobacter nicotinovorans biotechnology for
neuro-pharmaceuticals production

  • Research project financed by the Ministry of Education and Scientific Research -  Executive Unit for Financing Higher Education, Research, Development and Innovation (UEFISCDI), contract no. 175PED/28.08.2017
  • Funding amount  - 475000 lei (aprox. 100 000 euros);
  • Funding period - 16 months (28.08.2017 - 31.12.2018).

Project summary:

    6-hidroxy-nicotine (6HNic), a naturally occurring metabolite of Arthrobacter nicotinovorans was shown to bind the nicotinic acetylcholine receptors and to modulate their function. Experimental tests using laboratory rats have shown the ability of 6HNic to cope with the acetylcholine depletion and to restore normal brain functions.
6HNic has been thereby identified as a high impact bio-pharmaceutical with application in the therapy of
neurodegenerative disorders associated with low acetylcholine levels.
The scope of the project is to develop a technology for the production of the neuroprotective agent 6HNic in an industrial-like environment and to test it at a pilot scale. For this, a genetically engineered Arthrobacter strain will be created by knocking-out specific genes using suicidal vectors. The mutant strain will be further accommodated to a bio-reactor and the conditions for optimum 6HNic production will be evaluated. The final goal is to formulate a microbial based biotechnology for the production of 6HNic ready to be transferred to the industrial environment.

Project members: 


  • Marius Mihăşan, PhD
Project coordinator, Biochemistry, Molec. Biol. More details...
  • Marius Ştefan, PostDoc
Microbiology, Immunology More details...
  • Lucian Hritcu, PhD, Habil.
Neurophysiology, Behavior More details...

PhDs and students

  • Paula Alexandra Postu
Biochemistry and Behavior
  • Boiangiu Răzvan
Molecular Biology, Biochemistry and Behavior

Position on offer - details UAIC  ANCS Jobs - position not available, occupied by Boiangiu Răzvan, PhD student

Project's objectives and activities:

List of publications supported by the project:
1. Mihasan, M.; Babii, C.; Aslebagh, R.; Channaveerappa, D.; Dupree, E.; Darie, C. C.,  Proteomics based analysis of the nicotine catabolism in Paenarthrobacter nicotinovorans pAO1, Scientific Reports, 2018, 8, Article number: 16239 [Fulltext]
2.  Mocanu, E.-M.; Mazarachi, A.-L., Mihasan, M. In vitro stability and antioxidant potential of the neuprotective metabolite 6-hydroxy-nicotine, Journal of Experimental and Molecular Biology, 2018, 19:52-58 [Fulltext]

Submitted or under review
Roderich Brandsch, Mihăşan Marius - A soil bacterial catabolic pathway on the move: transfer of nicotine catabolic genes between Arthrobacter genus megaplasmids and invasion by mobile elements, Submitted to Journal of Molecular Evolution on 23.09.2018, Currently under review.

Conferences and posters - full list as pdf file is available here
Book Chapters: Lucian Hritcu, Marius Mihasan - Chapter 21: 6-Hydroxy-L-Nicotine and Memory Impairment, in Neuroscience of Nicotine, Elsevier 2019, in Press.

Patent: A patent for a biotechnology for production 6HNIc using have been submitted to OSIM Reg. no. A/01088/11.12.2018 .


Project manager:

Marius Mihăşan, PhD

Adress : Room B228, Biochemistry and Molecular Biology Laboratory, Faculty of Biology, Alexandru I Cuza University of Iasi, Carol I B-vd., No. 20A, Iaşi, 700506, Romania

E-mail :
Phone :   40(0)232201102 - 2434
Fax :         40(0)232201472
Further details: here

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