Associate Professor
Department of Biotechnology and Molecular Sciences
Via J.H. Dunant 3 - 21100 Varese - Italy
Tel: +39 (0)332 421546
Fax: +39 (0)332 421500
E-mail: flavia.marinelli@uninsubria.it

Flavia Marinelli studied at Rome and Pisa Universities where she obtained respectively a Laurea in Biology in the 1986 and a PhD in Chemistry in the 1991. Her studies focused on the cultivation of microbes and plant cells and on the chemistry and genetics of their secondary metabolites.
After a post-doc period at the Freiburg University in Germany, she joined the Lepetit Antinfective Research Center of the pharmaceutical firm Marion Merrell Dow, as Researcher devoted to the genetic improvement of antibiotic producing microbes.

In the 1995, she was appointed as the Director of the Microbial Isolation and  Fermentation Group first for Lepetit, then for Biosearch Italia and later on for Vicuron Pharmaceuticals. For more than ten years she has worked on the industrial microbiology and the genetics of filamentous microorganisms, mainly actinomycetes, producing new antibiotics. She has been also responsible of the Microbial Collection and of the Fermentation Pilot Plant.

In the 1996,  she was one of the eight founders of  Biosearch Italia, the first Italian biotechnology company quoted at Nuovo Mercato, Italy  and then at Nasdaq, USA,  and member of the first Board of Directors.

In the 2003-2004 she was  Contractor Professor of Chemistry and Biotechnology of Fermentation at University of Insubria. On 30th January 2004 she has appointed as  Associate Professor of Chemistry and Biotechnology of   Fermentation in the Department of Biotechnology and Molecular Sciences at University of Insubria.

She has built many national and international research cooperations: Prof.H.J.Tramper, Wageningen Agricultural University, Olanda; Prof. Eliora Ron, Microbiology, Tel Aviv University, Israele; Prof.F.Molinari Distam,Università di Milano; Prof.J. Swings, University of Ghent, Belgium: Prof. A.Wilmotte, University of Liege, Belgium; Prof.M.Tredici, Università di Firenze; Prof-M.Bibb, JohnInnes Institute, Norwich, UK; Prof.R.Kroppenstedt , DSMZ, Braunschweig, Germany.

She has been part of the EC consortia: MICROMAT BIO4-CT98-0040 “Biodiversity of microbial  mats in Antartica” and ACTAPHARM  QLRT-2001-01783 “Novel sources of actinomycetes diversity for detection of antimicrobial agents with pharmaceutical applications”.

She has written 46 internationally refereed  papers; she is co-inventor of four patents and has presented more than 80 lectures, abstracts, posters to national and international congresses.

Member of:
-Società Italiana di Microbiologia Generale e Biotecnologie Microbiche (SIMGBM)
-Society for Industrial Microbiology (SIM), USA
-American Society for Microbiology (ASM), USA
-World Federation of Culture Collections
- European  Federation of Biotechnology (EFB)

Since 2004, elected as representative of Industrial Microbiology in the  Board of SIMGBM.
Twice she has been called by EC as Expert for evaluation of research and development projects in biotechnological productions.
Recently she has been nominated by the Belgian Science Policy Office as foreign Expert for the evaluation of "Belgian Coordinated Collection of Microorganisms".

Fermentation Biotechnology Unit has been recently started up following the joining of Prof. Flavia Marinelli since January 2005.
The Fermentation and Microbiology labs are being installed and three new fermentors of 3 liter working volume are operative, flanking the 15 liter one already in use for protein production. The aim of the unit is to develop research projects mainly devoted to the biotechnological exploitation of uncommon and /or newly isolated and /or industrially relevant microrganisms, with a particular focus on actinomycetes. In parallel, the research unit is involved in the optimization and process development for protein production by native or heterologous hosts.

Microbial products are still unsurpassed in their ability to provide novel and unpredictable molecular diversity able to face the concomitant evolution of pathogen resistant strategies and complexity of biological targets. On the other hand it is commonly agreed that less than 1% of microbial species living on the Earth have been identified till now and probably much less can be easily cultivated and maintained in culture collections.

By accessing to peculiar habitats (from Antarctic lake mats to Israeli desert sands) and by employing selective isolation protocols, novel bacterial species belonging to biotechnologically relevant microbial groups, first of all actinomycetes, followed by myxobacteria and cyanobacteria have been isolated by Flavia Marinelli and her collaborators.
Novel metabolic pathways and products are been discovering in some of these organisms and their elucidation together with the development of cultivation methods and fermentation process represents a main interest of the lab. For two lipoglycopepetide antibiotics produced by two different actinomycetes, we are studying the self-resistance mechanisms, condition sine qua non for the antibiotic production and for its improvement. Interestingly the resistance genetic determinants and the phenotypes resemble and probably originated those described in the target pathogens, i.e. enterococci and staphylococci.

For other recently discovered antibacterials not only the chemical structure, but also the mechanism of action seems novel and promising for generating novel drugs. Novel species of actinomycetes have been recently employed to perform specific bioconversion of industrial interest such as the enantioselective hydrolysis of 1,2-O-isopropylidene glycerol esters to obtain the solketal, an important chiral building block for the synthesis of many optically active compounds, such as glycerophospholipids, beta-blockers, prostaglandins and leukotrienes. Bioconversion processes for regio-stereo specificity modification of complex antibiotic molecules such as lipoglico- peptides and depsipeptides have been optimized from the lab scale to the pilot plant reactors.

Actinomycetes can be used as free or immobilized cells, metabolically active or resting, or as a source of partially purified extracts, in batch or continuous reactors.
In particular the removal of one mannose unit from ramoplanin is carried out by a novel specie of Streptomyces isolated form soil, and the deacylation of teicoplanin-like molecules is performed by a group of actinomycetes selected among the producers of the same chemical class of antibiotics.

Flavia Marinelli holds the following courses:
- Chemistry and Biotechnology of Fermentations for Biotechnologists -I level, 5CFU
- Biotechnology of Fermentations for Biotechnologists -II level, 4CFU
- Production of Recombinant Proteins for Biotechnologists -II level, 2CFU
- Engineering Biotechnology for Biotechnologists- II level, 2CFU
- Applicative Microbiology for Engineers -I Level, 1.5 CFU

Flavia Marinelli joins the Professor commission for PhD fellows In Analysis, Managament and Protecion of Biodiversity.
She has been the supervisor of many graduate and PhD students, participating also as international referee in PhD dissertations at Ghent, Liege and Wageningen universities.
She was also involved in teaching PhD students in industrial microbiology.

F.Marinelli, S.Stella, N.Montanini, F.Le Monnier, L.Cavaletti, E.Selva (1995) Bioconversion capacity of Streptomyces sp.GE44282, a producer of the antibiotics heneicomycin and aurodox. Journal of Industrial Microbiology 15: 49-54.

F.Marinelli, L.Gastaldo, G.Toppo, C.Quarta (1996) Antibiotic GE37468A: a new inhibitor of bacterial protein synthesis. III.Strain and fermentation study. J.Antibiotics 49:880-885.

F.Marinelli, U.Zanelli , V.Nuti Ronchi (1996) Toxicity of 6-methoxymellein and 6-hydroxymellein to the producing carrot cells. Phytochemistry 42: 641-643.

L.Gastaldo,F. Marinelli, E.Restelli, C.Quarta (1996). Improvement of the kirromycin fermentation by resin addition. Journal of Industrial Microbiology 16:305-308.

A.Borghi, L.Cavaletti, F.Sponga, N.Montanini, W.Pollini, C.Quarta, F.Marinelli. The microbial product library for high-throughput screening at Lepetit Research Center (1998) in: New Frontiers in Screening for Microbial Biocatalysts Edited by K.Kieslich et al. Elseviers Science Publisher B.V, Amsterdam, pag: 235-238

S.Jovetic, J.Tramper, F.Marinelli (1998) Biotransformation of the lipoglycopeptide A40926 with immobilized cells of Actinoplanes teichomyceticus.-In situ supply of nutrients. Enzyme and Microbial Technology 22:117-121.

D.Zanette, W.Dundon, A.Soffientini, C.Sottani, F.Marinelli, A.Akeson, E.Sarubbi (1998) Human IL-1 receptor antagonist from Escherichia coli: Large-scale microbial growth and protein purification. Journal of Biotechnology 64: 187-196.

F.Sponga, L.Cavaletti, A.Lazzarini, A.Borghi, I.Ciciliato, D.Losi, F.Marinelli (1999) Biodiversity and potentials of marine-derived microorganisms. In: Progress in Industrial Microbiology35 Edited by R.Osinga et al., Elseviers Science Publisher B.V, Amsterdam, pag: 65-69

F.Sponga, L.Cavaletti, A.Lazzarini, A.Borghi, I.Ciciliato, D.Losi, F.Marinelli (1999) Biodiversity and potentials of marine-derived microorganisms. Journal of Biotechnology 70:65-69

R.Gandolfi, F. Marinelli, A.Lazzarini, F.Molinari, (2000) Cell-bound and extracellular carboxylesterases from Streptomyces: hydrolytic and synthetic activities. Journal of Applied Microbiology 89: 870-875.

A.Lazzarini, L.Cavaletti, G.Toppo and F.Marinelli (2000) Rare genera of actinomycetes as potential producers of new antibiotics. Antonie van Leeuwenhoek 78:399-405.

S.Jovetic, H.H. Beeftink, J.Tramper, F.Marinelli (2001) Diffusion of (de)acylated antibiotic A40926 in alginate and carrageenan beads with or without cells and /or soybean meal. Enzyme and Microbial Technology 28: 510-514.

M.J.Butler, P.Bruheim, S.Jovetic, F.Marinelli, P.W.Posta, M.J.Bibb (2002) Engineering of primary carbon metabolism for improved antibiotic production in Streptomyces lividans. Applied and Environmental Microbiology 68: 4731-4739

S.Jovetic, L.de Bresser, J.Tramper, F.Marinelli (2003) Deacylation of antibiotic A40926 by immobilized Actinoplanes teichomyceticus cells in an internal-loop-air-lift bioreactor. Enzyme and Microbial Technology 32: 546-552.

L.Gastaldo and F.Marinelli (2003) Changes in GE2270 antibiotic production in Planobispora rosea through modulation of methylation metabolism. Microbiology 149: 1523-1532

F.Beltrametti, A.Lazzarini, C. Brunati, E. Selva, F. Marinelli (2003) Production of demannosyl-A40926 by a Nonomuria sp. ATCC 39727 mutant strain. Journal of Antibiotics 56: 310-313

M.J.Butler, E.Takano, P.Bruheim, S.Jovetic, F.Marinelli, M.J.Bibb (2003) Deletion of scbA enhances antibiotic production in Streptomyces lividans 132. Applied Microbiology and Biotechnology, 61:512-516

F. Beltrametti, A. Lazzarini, C.Brunati, A. Marazzi, S. Jovetic, E. Selva, F. Marinelli (2003) Production and Characterization of monochlorinated and dechlorinated A40926 derivatives. Journal of Antibiotics 56:773-782

I.Ciciliato, E.Corti, E.Sarubbi, S.Stefanelli, N.Montanini, F.Marinelli, M.Kurz, E.Selva Antibiotics GE 23077, pharmaceutically acceptable salts and compositions, and use thereof. US Patent No 6,586,393 Granted Jul.1, 2003; European Patent Application No00126618.8 Filed Dec.12,2000.

E.Selva, F.Marinelli, D.Losi, L.Cavaletti, A.Lazzarini, A.Marazzi Antibiotics GE 81112 factors A, B, B1, pharmaceutically acceptable salts and compositions, and use thereof. WO 03/046192 Granted Jun 6, 2003; European Patent Application No PCT/EPO2/11113 Filed Oct.4,2002

M.Brunati, F.Marinelli, C.Bertolini, R.Gandolfi, D.Daffonchio, F.Molinari (2004) Biotransformations of cinnamic and ferulic acid with actinomycetes. Enzyme Microbial Techonology 34:3-9

F. Beltrametti, S.Jovetic, M.Feroggio, L.Gastaldo, E.Selva , F.Marinelli (2004) Valine influences production and complex composition of glycopeptide antibiotic A40926 in fermentation of Nonomuraea sp. ATCC 39727. Journal of Antibiotics 57:37-44

I.Ciciliato, E.Corti, E.Sarubbi, S.Stefanelli, L.Gastaldo, N.Montanini, M.Kurz, D.Losi,  F.Marinelli, E.Selva (2004) Antibiotics GE23077, novel inhibitors of bacterial RNA polymerase I. Taxonomy, Isolation and Characterization. Journal of Antibiotics 57:210-217

F. Marinelli, M.Brunati, F.Sponga I.Ciciliato, D.Losi, S. Van Trappen, J.Mergaert, J.Swings, E. Göttlich, G.S. de Hoog, J.L. Rojas, O. Genilloud, (2004) Biotechnological exploitation of heterotrophic bacteria and filamentous fungi isolated from benthic mats of Antarctic lakes. In: Microbial Genetic Resources and Biodiscovery Edited by I. Kurtböke and J.Swings. Queensland Complete Printing Services, Queesland, Australia pag: 163-184

D.Losi, L.Cavaletti, A.Lazzarini, P.Candiani, F.Castiglioni, F.Marinelli Antibiotics ID 97518 , pharmaceutically acceptable salts and compositions, and use thereof. EP 1 481 986 A1, Granted Dec 1, 2004; European Patent Application. No03012422.6. Filed May 30, 2003

F. Gaspari, Y. Paitan, M. Mainini, D. Losi, E. Z. Ron, F. Marinelli (2005) Myxobacteria isolated in Israel as potential source of new anti-infectives. Journal of Applied Microbiology 98: 429-439.

F.Molinari, D.Romano, R.Gandolfi, R.M. Kroppenstedt, F.Marinelli (2005) Newly isolated Streptomyces spp. as enantioselective biocatalysts: hydrolysis of 1,2-O-isopropylidene glycerol racemic esters. In press, Journal of Applied Microbiology

S.Jovetìc, F.Marinelli, J. Tramper (2005) Continuous biotransformation of glycopeptide antibiotic A40926 in a cascade of three airlift bioreactors using immobilizedActinoplanes teichomyceticus cells. In press, Enzyme and Microbial Technology

M.Brunati , A.Bava, F.Marinelli, G.Lancini (2005) Influence of leucine and valine on ramoplanin production by Actinoplanes sp.ATCC 33076. Journal of Antibiotics 58: 473-478.

A.Lazzarini, L.Gastaldo, P.Candiani, I.Ciciliato, D.Losi, F.Marinelli, E.Selva, F.Parenti Antibiotics 107,891, its factor A1 and A2, pharmaceutically acceptable salts and compositions, and use thereof. WO 2005/014628 A1 Granted Feb17, 2005. European Patent Application. No 03016306.7. Filed Jul 18, 2003

S.Jovetìc, F.Marinelli, J. Tramper (2006) Continuous biotransformation of glycopeptide antibiotic A40926 in a cascade of three airlift bioreactors using immobilized Actinoplanes teichomyceticus cells. Enzyme and Microbial Technology, 38:34-39

F.Beltrametti, Rossi, E.Selva, F.Marinelli (2006) Antibiotic production improvement in the rare actinomycete Planobsipora rosea by selection of resistance mutations to the aminoglycosides streptomycin and gentamycin and to rifamycin. Journal of Industrial Microbiology and Biotechnology, 33:283-288

L.Brandi, A. Lazzarini, L. Cavaletti, M. Abbondi, E.Corti, I. Ciciliato, L. Gastaldo, A. Marazzi, M. Feroggio, A. Fabbretti, A. Maio, L.Colombo, S. Donadio, F. Marinelli, D.Losi, C. O.Gualerzi, E. Selva (2006), Novel tetrapeptide inhibitors of bacterial protein synthesis produced by a Streptomyces sp. Biochemistry, 45:3700-3710

A. Taton, S. Grubisic, D. Ertz, D. A. Hodgson, R. Piccardi, N. Biondi, M.Tredici, M.Mainini, D. Losi, F. Marinelli, A. Wilmotte (2006) Polyphasic study of Antarctic cyanobacterial strains. Journal of Phycology , 42:1257-1270