Prof. Raphael Lamed

מקרוביולוגיה מולקולרית אמריטוס
Prof. Raphael Lamed
Phone: 03-6407514
Another phone: 03-6407515
Fax: 03-6409407
Office: Green - Biotechnology, 140

CV

Education:

1969 B.Sc. Hebrew University, Jerusalem, Israel, Chemistry

1971 M.Sc Hebrew University, Jerusalem, Israel, Biological Chemistry

1975 Ph.D. Weizmann Institute of Science, Rehovot, Israel, Biochemistry

1977 Postdoc, University of Wisconsin, USA, Pharmacology

1978 Postdoc, University of Wisconsin, USA, Microbiology

 

 

Academic and Professional Experience:

1971-1972 Biophysics, Weizmann Institute of Science, Rehovot, Israel

1975-1977 Biotechnology, Weizmann Institute of Science, Rehovot, Israel

1979-1980 Biotechnology, General Electric R&D, Schenectady, NY

1987-1988 Sabbatical, Biotechnology, Michigan State University, USA

1991-1993 Teaching fellow, Biomedical Engineering, Technion, Haifa, Israel

1993-1995 Sabbatical, Biophysics, Yale University, USA

1980--present.  Department of Microbiology & Biotechnology, Tel-Aviv University, Tel Aviv, Israel

 

 

Professor Raphael Lamed is a member of the TAU Research Center for Renewable Energy

 

Research Interests

My research interests include:

  • Biomass to Biofuels:  Our interest and research is in conversion of biomass to biofuels and also useful intermediate commodity chemicals.The ability of cellulolytic bacteria to degrade cellulose can potentially be used for the degradation of organic matter in garbage and for production of biofuels from waste, which is a major environmental challenge of our time. We are mainly involved in basic scientific research for a clean energy future and an alternative energy research initiative.  We have developed a novel approach to mimic a natural multi-enzyme protein complex – the cellulosome – and have achieved a new generation of designer cellulosomes for conversion of the biomass (ligno-cellulosic) to value added products. Many of our research efforts have been recognized and cited by bio-based industries in their standard operation protocols.
  • Bacteria can degrade cellulose via large multi-enzyme complexes – Cellulosomes:The cellulases of many cellulolytic bacteria were shown by us to be organized into discrete multienzyme complexes, called  cellulosomes.  The cellulosomes are associated with the cell surface and mediate cell attachment to the insoluble substrate and degrade it into soluble products which are then absorbed by the cell. 
  • Microbial Biomass Sensors: A Novel Transcription Regulatory System in Cellulolytic Bacteria:  Some cellulolytic bacteria, such as Clostridium thermocellum produce extracellular multi-enzyme systems, highlighted by the cellulosome complex, for degradation of plant cell wall polysaccharides and cellulosic wastes. Such bacteria can produce over 70 different enzyme components, which include cellulases, xylanases, mannanases, arabinases, galactanases, carbohydrate esterases and pectin-degrading enzymes. However, it is not known how the bacterium decides which enzymes are incorporated into the cellulosome.
  • X-ray crystallography and 3-D structure solution:  We are focusing on the crystallization and elucidation of the 3D structures of CBMs, enzymes, cellulosomal components and parts of the biomass-sensing regulatory system. Resolving the 3D protein structure will help us to reveal its function and mode of action. Moreover it sheds light on the mechanism of protein-protein and protein-substrate interactions. 

 

For a full research description (pdf)

Recent Publications

Salama-Alber O, Jobby MK, Chitayat S, Smith SP, White BA, Shimon LJ, Lamed R, Frolow F, Bayer EA. Atypical cohesin-dockerin complex responsible for cell-surface attachment of cellulosomal components: binding fidelity, promiscuity, and structural buttresses. J Biol Chem. 2013 Apr 11. [Epub ahead of print] PubMed PMID: 23580648.

 

Levy-Assaraf M, Voronov-Goldman M, Rozman Grinberg I, Weiserman G, Shimon LJ, Jindou S, Borovok I, White BA, Bayer EA, Lamed R, Frolow F. Crystal structure of an uncommon cellulosome-related protein module from Ruminococcus flavefaciens that resembles papain-like cysteine peptidases . PLoS One. 2013;8(2):e56138. doi: 10.1371/journal.pone.0056138. Epub 2013 Feb 14. PubMed PMID: 23457513; PubMed Central PMCID: PMC3573020.

 

Moraïs S, Morag E, Barak Y, Goldman D, Hadar Y, Lamed R, Shoham Y, Wilson DB, Bayer EA. Deconstruction of lignocellulose into soluble sugars by native and designer cellulosomes. MBio. 2012 Dec 11;3(6). doi:pii: e00508-12. 10.1128/mBio.00508-12. PubMed PMID: 23232718; PubMed Central PMCID: PMC3520109.

 

Slutzki M, Barak Y, Reshef D, Schueler-Furman O, Lamed R, Bayer EA. Indirect ELISA-based approach for comparative measurement of high-affinity cohesin-dockerin interactions. J Mol Recognit. 2012 Nov;25(11):616-22. doi: 10.1002/jmr.2178. PubMed PMID: 23108621.

 

Moraïs S, Barak Y, Lamed R, Wilson DB, Xu Q, Himmel ME, Bayer EA. Paradigmatic status of an endo- and exoglucanase and its effect on crystalline cellulose degradation. Biotechnol Biofuels. 2012 Oct 24;5(1):78. doi: 10.1186/1754-6834-5-78. PubMed PMID: 23095278; PubMed Central PMCID: PMC3502487.

 

Salama-Alber O, Gat Y, Lamed R, Shimon LJ, Bayer EA, Frolow F. Crystallization and preliminary X-ray characterization of a type III cohesin-dockerin complex from the cellulosome system of Ruminococcus flavefaciens. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Sep 1;68(Pt 9):1116-9. doi: 10.1107/S1744309112033088. Epub 2012 Aug 31. PubMed PMID: 22949209; PubMed Central PMCID: PMC3433212.

 

Moraïs S, Lamed R, Bayer EA. Affinity electrophoresis as a method for determining substrate-binding specificity of carbohydrate-active enzymes for soluble polysaccharides. Methods Mol Biol. 2012;908:119-27. doi: 10.1007/978-1-61779-956-3_12. PubMed PMID: 22843395.

 

Fraiberg M, Borovok I, Weiner RM, Lamed R, Bayer EA. Bacterial cadherin domains as carbohydrate binding modules: determination of affinity constants to insoluble complex polysaccharides. Methods Mol Biol. 2012;908:109-18. doi: 10.1007/978-1-61779-956-3_11. PubMed PMID: 22843394.

 

Yaniv O, Jindou S, Frolow F, Lamed R, Bayer EA. A simple method for determining specificity of carbohydrate-binding modules for purified and crude insoluble polysaccharide substrates. Methods Mol Biol. 2012;908:101-7. doi: 10.1007/978-1-61779-956-3_10. PubMed PMID: 22843393.

 

Yaniv O, Petkun S, Shimon LJ, Bayer EA, Lamed R, Frolow F. A single mutation reforms the binding activity of an adhesion-deficient family 3 carbohydrate-binding module. Acta Crystallogr D Biol Crystallogr. 2012 Jul;68(Pt 7):819-28. doi: 10.1107/S0907444912013133. Epub 2012 Jun 15. PubMed PMID: 22751667.

 

Gefen G, Anbar M, Morag E, Lamed R, Bayer EA. Enhanced cellulose degradation by targeted integration of a cohesin-fused β-glucosidase into the Clostridium thermocellum cellulosome. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10298-303. doi: 10.1073/pnas.1202747109. Epub 2012 Jun 11. PubMed PMID: 22689961; PubMed Central PMCID: PMC3387075.

 

Dassa B, Borovok I, Lamed R, Henrissat B, Coutinho P, Hemme CL, Huang Y, Zhou J, Bayer EA. Genome-wide analysis of acetivibrio cellulolyticus provides a blueprint of an elaborate cellulosome system. BMC Genomics. 2012 May 30;13:210. doi: 10.1186/1471-2164-13-210. PubMed PMID: 22646801; PubMed Central PMCID: PMC3413522.

 

Brown SD, Lamed R, Morag E, Borovok I, Shoham Y, Klingeman DM, Johnson CM, Yang Z, Land ML, Utturkar SM, Keller M, Bayer EA. Draft genome sequences for Clostridium thermocellum wild-type strain YS and derived cellulose adhesion-defective mutant strain AD2. J Bacteriol. 2012 Jun;194(12):3290-1. doi: 10.1128/JB.00473-12. PubMed PMID: 22628515; PubMed Central PMCID: PMC3370843.

 

Slutzki M, Ruimy V, Morag E, Barak Y, Haimovitz R, Lamed R, Bayer EA. High-throughput screening of cohesin mutant libraries on cellulose microarrays. Methods Enzymol. 2012;510:453-63. doi: 10.1016/B978-0-12-415931-0.00024-0. PubMed PMID: 22608741.

 

Vazana Y, Moraïs S, Barak Y, Lamed R, Bayer EA. Designer cellulosomes for enhanced hydrolysis of cellulosic substrates. Methods Enzymol. 2012;510:429-52. doi: 10.1016/B978-0-12-415931-0.00023-9. PubMed PMID: 22608740.

 

Slutzki M, Barak Y, Reshef D, Schueler-Furman O, Lamed R, Bayer EA. Measurements of relative binding of cohesin and dockerin mutants using an advanced ELISA technique for high-affinity interactions. Methods Enzymol. 2012;510:417-28. doi: 10.1016/B978-0-12-415931-0.00022-7. PubMed PMID: 22608739.

 

Yaniv O, Frolow F, Levy-Assraf M, Lamed R, Bayer EA. Interactions between family 3 carbohydrate binding modules (CBMs) and cellulosomal linker peptides. Methods Enzymol. 2012;510:247-59. doi: 10.1016/B978-0-12-415931-0.00013-6. PubMed PMID: 22608730.

 

Anbar M, Gul O, Lamed R, Sezerman UO, Bayer EA. Improved thermostability of Clostridium thermocellum endoglucanase Cel8A by using consensus-guided mutagenesis. Appl Environ Microbiol. 2012 May;78(9):3458-64. doi: 10.1128/AEM.07985-11. Epub 2012 Mar 2. PubMed PMID: 22389377; PubMed Central PMCID: PMC3346478.

 

Moraïs S, Salama-Alber O, Barak Y, Hadar Y, Wilson DB, Lamed R, Shoham Y, Bayer EA. Functional association of catalytic and ancillary modules dictates enzymatic activity in glycoside hydrolase family 43 β-xylosidase. J Biol Chem. 2012 Mar 16;287(12):9213-21. doi: 10.1074/jbc.M111.314286. Epub 2012 Jan 23. PubMed PMID: 22270362; PubMed Central PMCID: PMC3308730.

 

Yaniv O, Halfon Y, Shimon LJ, Bayer EA, Lamed R, Frolow F. Structure of CBM3b of the major cellulosomal scaffoldin subunit ScaA from Acetivibrio cellulolyticus. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Jan 1;68(Pt 1):8-13. doi: 10.1107/S174430911104807X. Epub 2011 Dec 24. PubMed PMID: 22232162; PubMed Central PMCID: PMC3253825.

 

Moraïs S, Barak Y, Hadar Y, Wilson DB, Shoham Y, Lamed R, Bayer EA. Assembly of xylanases into designer cellulosomes promotes efficient hydrolysis of the xylan component of a natural recalcitrant cellulosic substrate. MBio. 2011 Nov 15;2(6). doi:pii: e00233-11. 10.1128/mBio.00233-11. Print 2011. PubMed PMID: 22086489; PubMed Central PMCID: PMC3221603.  

 

Brulc JM, Yeoman CJ, Wilson MK, Berg Miller ME, Jeraldo P, Jindou S, Goldenfeld N, Flint HJ, Lamed R, Borovok I, Vodovnik M, Nelson KE, Bayer EA, White BA. Cellulosomics, a gene-centric approach to investigating the intraspecific diversity and adaptation of Ruminococcus flavefaciens within the rumen. PLoS One. 2011;6(10):e25329. doi: 10.1371/journal.pone.0025329. Epub 2011 Oct 17. PubMed PMID: 22043282; PubMed Central PMCID: PMC3197198.  

 

Berg Miller ME, Yeoman CJ, Chia N, Tringe SG, Angly FE, Edwards RA, Flint HJ, Lamed R, Bayer EA, White BA.Phage-bacteria relationships and CRISPR elements revealed by a metagenomic survey of the rumen microbiome. Environ Microbiol. 2012 Jan;14(1):207-27. doi: 10.1111/j.1462-2920.2011.02593.x. Epub 2011 Oct 17. PubMed PMID: 22004549.  

 

Caspi J, Barak Y, Haimovitz R, Gilary H, Irwin DC, Lamed R, Wilson DB, Bayer EA. Thermobifida fusca exoglucanase Cel6B is incompatible with the cellulosomal mode in contrast to endoglucanase Cel6A. Syst Synth Biol. 2010 Sep;4(3):193-201. doi: 10.1007/s11693-010-9056-1. Epub 2010 Apr 30. PubMed PMID: 21886683; PubMed Central PMCID: PMC2955202.  

 

Yaniv O, Shimon LJ, Bayer EA, Lamed R, Frolow F. Scaffoldin-borne family 3b carbohydrate-binding module from the cellulosome of Bacteroides cellulosolvens: structural diversity and significance of calcium for carbohydrate binding. Acta Crystallogr D Biol Crystallogr. 2011 Jun;67(Pt 6):506-15. doi: 10.1107/S0907444911011322. Epub 2011 May 12. PubMed PMID: 21636890.  

 

Moraïs S, Barak Y, Caspi J, Hadar Y, Lamed R, Shoham Y, Wilson DB, Bayer EA. Cellulase-xylanase synergy in designer cellulosomes for enhanced degradation of a complex cellulosic substrate. MBio. 2010 Dec 14;1(5). doi:pii: e00285-10. 10.1128/mBio.00285-10. PubMed PMID: 21157512; PubMed Central PMCID: PMC2999897.  

 

Demishtein A, Karpol A, Barak Y, Lamed R, Bayer EA. Characterization of a dockerin-based affinity tag: application for purification of a broad variety of target proteins. J Mol Recognit. 2010 Nov-Dec;23(6):525-35. doi: 10.1002/jmr.1029. PubMed PMID: 21038354.  

 

Fraiberg M, Borovok I, Bayer EA, Weiner RM, Lamed R. Cadherin domains in the polysaccharide-degrading marine bacterium Saccharophagus degradans 2-40 are carbohydrate-binding modules. J Bacteriol. 2011 Jan;193(1):283-5. doi: 10.1128/JB.00842-10. Epub 2010 Oct 29. PubMed PMID: 21036994; PubMed Central PMCID: PMC3019924.  

 

Voronov-Goldman M, Lamed R, Noach I, Borovok I, Kwiat M, Rosenheck S, Shimon LJ, Bayer EA, Frolow F.Noncellulosomal cohesin from the hyperthermophilic archaeon Archaeoglobus fulgidus. Proteins. 2011 Jan;79(1):50-60. doi: 10.1002/prot.22857. Epub 2010 Oct 15. PubMed PMID: 20954171.  

 

Nataf Y, Bahari L, Kahel-Raifer H, Borovok I, Lamed R, Bayer EA, Sonenshein AL, Shoham Y. Clostridium thermocellum cellulosomal genes are regulated by extracytoplasmic polysaccharides via alternative sigma factors. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18646-51. doi: 10.1073/pnas.1012175107. Epub 2010 Oct 11. PubMed PMID: 20937888; PubMed Central PMCID: PMC2972930.  

 

Bahari L, Gilad Y, Borovok I, Kahel-Raifer H, Dassa B, Nataf Y, Shoham Y, Lamed R, Bayer EA. Glycoside hydrolases as components of putative carbohydrate biosensor proteins in Clostridium thermocellum. J Ind Microbiol Biotechnol. 2011 Jul;38(7):825-32. doi: 10.1007/s10295-010-0848-9. Epub 2010 Sep 6. PubMed PMID: 20820855.  

 

Rincon MT, Dassa B, Flint HJ, Travis AJ, Jindou S, Borovok I, Lamed R, Bayer EA, Henrissat B, Coutinho PM, Antonopoulos DA, Berg Miller ME, White BA. Abundance and diversity of dockerin-containing proteins in the fiber-degrading rumen bacterium, Ruminococcus flavefaciens FD-1. PLoS One. 2010 Aug 30;5(8):e12476. doi: 10.1371/journal.pone.0012476. PubMed PMID: 20814577; PubMed Central PMCID: PMC2930009.  

 

Kahel-Raifer H, Jindou S, Bahari L, Nataf Y, Shoham Y, Bayer EA, Borovok I, Lamed R. The unique set of putative membrane-associated anti-sigma factors in Clostridium thermocellum suggests a novel extracellular carbohydrate-sensing mechanism involved in gene regulation. FEMS Microbiol Lett. 2010 Jul 1;308(1):84-93. doi: 10.1111/j.1574-6968.2010.01997.x. Epub 2010 Apr 23. PubMed PMID: 20487018.  

 

Moraïs S, Heyman A, Barak Y, Caspi J, Wilson DB, Lamed R, Shoseyov O, Bayer EA. Enhanced cellulose degradation by nano-complexed enzymes: Synergism between a scaffold-linked exoglucanase and a free endoglucanase. J Biotechnol. 2010 Jun;147(3-4):205-11. doi: 10.1016/j.jbiotec.2010.04.012. Epub 2010 May 7. PubMed PMID: 20438772.

 

Moraïs S, Barak Y, Caspi J, Hadar Y, Lamed R, Shoham Y, Wilson DB, Bayer EA. Contribution of a xylan-binding module to the degradation of a complex cellulosic substrate by designer cellulosomes. Appl Environ Microbiol. 2010 Jun;76(12):3787-96. doi: 10.1128/AEM.00266-10. Epub 2010 Apr 16. PubMed PMID: 20400556; PubMed Central PMCID: PMC2893491.  

 

Noach I, Levy-Assaraf M, Lamed R, Shimon LJ, Frolow F, Bayer EA. Modular arrangement of a cellulosomal scaffoldin subunit revealed from the crystal structure of a cohesin dyad. J Mol Biol. 2010 Jun 4;399(2):294-305. doi: 10.1016/j.jmb.2010.04.013. Epub 2010 Apr 13. PubMed PMID: 20394754.  

 

Vazana Y, Moraïs S, Barak Y, Lamed R, Bayer EA. Interplay between Clostridium thermocellum family 48 and family 9 cellulases in cellulosomal versus noncellulosomal states. Appl Environ Microbiol. 2010 May;76(10):3236-43. doi: 10.1128/AEM.00009-10. Epub 2010 Mar 26. PubMed PMID: 20348303; PubMed Central PMCID: PMC2869131.  

 

Petkun S, Jindou S, Shimon LJ, Rosenheck S, Bayer EA, Lamed R, Frolow F. Structure of a family 3b' carbohydrate-binding module from the Cel9V glycoside hydrolase from Clostridium thermocellum: structural diversity and implications for carbohydrate binding. Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):33-43. doi: 10.1107/S0907444909043030. Epub 2009 Dec 21. PubMed PMID: 20057047.  

 

Fraiberg M, Borovok I, Weiner RM, Lamed R. Discovery and characterization of cadherin domains in Saccharophagus degradans 2-40. J Bacteriol. 2010 Feb;192(4):1066-74. doi: 10.1128/JB.01236-09. Epub 2009 Dec 18. PubMed PMID: 20023015; PubMed Central PMCID: PMC2812970.

 

Caspi J, Barak Y, Haimovitz R, Irwin D, Lamed R, Wilson DB, Bayer EA. Effect of linker length and dockerin position on conversion of a Thermobifida fusca endoglucanase to the cellulosomal mode. Appl Environ Microbiol. 2009 Dec;75(23):7335-42. doi: 10.1128/AEM.01241-09. Epub 2009 Oct 9. PubMed PMID: 19820154; PubMed Central PMCID: PMC2786427.  

 

Berg Miller ME, Antonopoulos DA, Rincon MT, Band M, Bari A, Akraiko T, Hernandez A, Thimmapuram J, Henrissat B, Coutinho PM, Borovok I, Jindou S, Lamed R, Flint HJ, Bayer EA, White BA. Diversity and strain specificity of plant cell wall degrading enzymes revealed by the draft genome of Ruminococcus flavefaciens FD-1. PLoS One. 2009 Aug 14;4(8):e6650. doi: 10.1371/journal.pone.0006650. PubMed PMID: 19680555; PubMed Central PMCID: PMC2721979.  

 

Wine Y, Cohen-Hadar N, Lamed R, Freeman A, Frolow F. Modification of protein crystal packing by systematic mutations of surface residues: implications on biotemplating and crystal porosity. Biotechnol Bioeng. 2009 Oct 15;104(3):444-57. doi: 10.1002/bit.22427. PubMed PMID: 19575413. 

 

Alber O, Noach I, Rincon MT, Flint HJ, Shimon LJ, Lamed R, Frolow F, Bayer EA. Cohesin diversity revealed by the crystal structure of the anchoring cohesin from Ruminococcus flavefaciens. Proteins. 2009 Nov 15;77(3):699-709. doi: 10.1002/prot.22483. PubMed PMID: 19544570.  

 

Noach I, Frolow F, Alber O, Lamed R, Shimon LJ, Bayer EA. Intermodular linker flexibility revealed from crystal structures of adjacent cellulosomal cohesins of Acetivibrio cellulolyticus. J Mol Biol. 2009 Aug 7;391(1):86-97. doi: 10.1016/j.jmb.2009.06.006. Epub 2009 Jun 6. PubMed PMID: 19501595.  

 

Burstein T, Shulman M, Jindou S, Petkun S, Frolow F, Shoham Y, Bayer EA, Lamed R. Physical association of the catalytic and helper modules of a family-9 glycoside hydrolase is essential for activity. FEBS Lett. 2009 Mar 4;583(5):879-84. doi: 10.1016/j.febslet.2009.02.013. Epub 2009 Feb 12. PubMed PMID: 19302786.  

 

Voronov-Goldman M, Noach I, Lamed R, Shimon LJ, Borovok I, Bayer EA, Frolow F. Crystallization and preliminary X-ray analysis of a cohesin-like module from AF2375 of the archaeon Archaeoglobus fulgidus. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Mar 1;65(Pt 3):275-8. doi: 10.1107/S1744309109002887. Epub 2009 Feb 26. PubMed PMID: 19255482; PubMed Central PMCID: PMC2650457.

 

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