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Center for Biocatalysis & Bioprocessing of Macromolecules (CBBM) 
at Rensselaer Polytechnic Institute (RPI)

A NATIONAL SCIENCE FOUNDATION INDUSTRY/UNIVERSITY COOPERATIVE RESEARCH CENTER

Biocatalysis encompasses a wide platform of chemistries that afford opportunities for innovative new products and processes. Hallmarks of biocatalysts are their ability to operate under mild conditions, with impressive selectivity, on a diverse range of natural and non-natural substrates. Enzyme immobilization is used to improve enzyme stability and activity creating robust catalysts for multi-cycle re-use and to optimize their function for current manufacturing equipment and processes. Rapid advances in biotechnology continues to decrease the time and resources required to engineer organisms to produce desired products in high titers as well as to engineer enzymes with increased thermal stability, efficiency and specificity. The Center works with its members to apply existing or develop new biocatalytic methods that solve short or long term challenges creating commercialization opportunities. Our technical focus is to develop a toolset of biocatalytic solutions that can be applied to problems in polymer science and surfactant technologies. To accomplish these objectives, the Center has assembled an impressive network of scientists both at and outside RPI that bring a broad range of experimental, computational, theoretical and analytical knowledge. Furthermore, members self-direct research to ensure that they maximize their return on investment.

Biocatalysis, Polymer, and Material Science Research at Rensselaer Polytechnic Insitute (RPI):

RPI is the home of the New York State Center for Polymer Synthesis. Dedicated in 1998, the center was created to continue a history that has impacted several generations of polymer scientists and led to breakthrough research through an early recognition of the importance of an interdisciplinary approach to the field. The facility houses advanced technology for the discovery, scale-up, processing, and evaluation of polymers and materials. The Center’s focus is grounded in three areas: innovative research, corporate and government partnerships, and undergraduate and graduate education. Polymer Chemistry Faculty are focused on biobased and sustainable polymer synthesis using both enzyme and chemical methods. The Center for Biotechnology & Interdisciplinary Studies (CBIS) The Center for Biotechnology & Interdisciplinary Studies serves as the primary focus of biotechnology research and training at RPI. Approaches taken by CBIS researchers include computational and experimental with focuses on biomolecular, cellular, and organismal levels. CBIS research is organized to facilitate understanding of fundamental principles in biology, chemistry, and the engineering sciences. Outcomes of this research includes new enzyme discovery, biophysical characterizations, re-engineering for improved catalytic activity and stability, studies of surface-enzyme interactions to optimize enzyme immobilization, fermentation process engineering, cell-free bioprocess design and biomaterials for therapeutic applications.

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NSF Center for Directed Assembly of Nanostructures: Major emphasis areas include how nanoscale building blocks are assembled to create new materials and novel devices that can be controlled and manipulated. The Center has been incorporating enzymes and other proteins in nanomaterials to create bioactive materials with antifouling or catalyst properties.

Center Vision:

We stand at the threshold of a revolution in the way Industry will look towards biologically based materials and processes. The launching of new products is increasingly dependent on cradle-to-grave assessments. Significant additional costs will be imposed on industry for the disposal of toxic chemicals and by-products. These considerations will accelerate the rate-of-change in the way that chemistry and processes are designed and conducted. Completely new methods will emerge that reach well beyond incremental improvements to the discovery of new paradigms in synthesis and processing. Biocatalysis, whether using isolated enzymes or whole cells, offers unique opportunities to meet the evolving needs of environmentally compatible processes. In reviewing the level of activity and knowledge in biocatalysis, we found a substantial effort in the development of low molar mass molecules but polymers have received much less attention. Also, For decades, the production of surfactants for an array of application areas such as agrochemicals, photo chemicals, oil field chemicals, construction materials, foodstuffs, adhesives, lubricants, metal working and mining has relied on the use of complex production processes. The Center will explore opportunities to develop biosurfactants that are safe, biodegradable, have high bio-based carbon content and have attractive physico-chemical properties. The Center will provide a cost-effective mechanism that enables scientists and engineers at Member companies to rapidly get up-to-speed in Biocatalysis and Bioprocessing, determine opportunities in the field, gain access to ideas and new technology, initiate projects of interest for which they did not have sufficient resources, and find business partners that complement their expertise.

WHY ENZYME-CATALYSIS?

Control of Structure – Enzyme selectivity can be directed towards the synthesis of unique surfactants, peptides, monomers, macromers and polymers. Functionality that would otherwise be difficult to achieve without protection-deprotection steps can be attained by regioselective transformations.

 

Simplicity of Reactions Over an Ever-Widening Range of Conditions - An important feature of biocatalytic reactions is the growing range of reaction conditions in which it can be performed. These include bulk systems, organic solvents, biphasic conditions, emulsions, and in supercritical fluids. 

 

Multistep Conversions in Aqueous Media: Whole-cell transformations convert low-cost materials to value-added products. Concepts of metabolic engineering used in combination with enzyme evolution provide powerful methods for the development of efficient microbial catalysts. 

 

Green Chemistry - The use of environmentally compatible methods for synthesis and processing is good business. Enzymes allow reductions in processing temperatures, provide metal-free safe catalysts, and convert multiple-step processes to one-pot reactions. They are also made and degraded by natural processes.

 

Protein Engineering - Incorporated diversity can be retrieved through structural constraints, phylogenetic diversity, random mutations or immunological constraints. Analysis of systematically varied sets of sequences is being applied to improve key enzymes under study within the Center. This strategy has the advantage of requiring orders of magnitude fewer variants than directed evolution methods, while not being constrained by structurally interpretable changes.

RESEARCH AREAS:

We are exploring how the diverse chemistries, mild reaction conditions and selectivity of enzymes can provide unique opportunities to develop new or improve synthetic routes to molecules and materials of industrial importance. The following summarizes Center research activities: 

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  • Lipases, cutinases, esterases, proteases, peroxidases, laccases, glycosidases and other enzymes families

  • Protein engineering

  • Enzyme characterization: thermo- and pH stability, post-translational modification, biochemical characterization, tendency to aggregate, etc.

  • Bioactive surfaces (e.g. antifouling, catalytic, etc.)

  • Metabolic engineering to efficiently produce high-value chemicals

  • Fatty acid bioconversions (e.g. w-hydroxy and w-carboxyfatty acids)

  • Enzyme-ink printing creating pre-determined surface patterns, microcontainers, and nanocontainers on biomaterials

  • New technologies for low-cost peptide synthesis using protease catalysis. Study of their potential use in metal binding, adhesion, self-assembly, and bioactivity.

  • Biosurfactants for uses in cosmetics, cleaning, antimicrobial agents, and as templates for directed material assembly

  • Chemical conversions of biobased building blocks to prepolymers, polymers, and surfactants.

  • Bioprocess engineering such as by using milli-reactor systems.

  • Enzyme immobilixation for enhanced enzyme activity and recycling

  • Enzyme 'triggered' processes

  • Innovative new bioresorbable polymers

  • Biomaterial-celle interactions

  • Bioactive nanocomposites for various functions such as anti-fouling surfaces

  • Developing biofibers

  • Functionalization of cellulose nanocrystals and their use in material applications.

  • Biopolishing and surface modification.

  • Reactive processing using enzyme-catalysis.

RESEARCH AREAS:

Plastics, elastomers, adhesives, coatings, macromers, functional prepolymers, nanocomposites, formulation ingredients (e.g. biosurfactants, peptides), polyurethanes, water-soluble polymers, surfactants, vinyl monomers, cosmetics, fine chemicals, nutraceuticals, agricultural materials, bioresorbable polymers, scaffolds for tissue engineering, protein therapeutics, oligopeptides functionalized surfaces.

CENTER STAFF:

The Center has assembled an impressive group of Faculty and Scientists from a wide-range of participating universities. Faculty, postdoctoral fellows and graduate students work in interdisciplinary teams. The following lists these participants, their affiliation and core research interests (in alphabetical order): 

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Dr. Kathryn Beers (micro-reactors and microfluidics) NIST; Professor George Belfort (proteinsurface interactions, protein aggregation, overcoming difficult protein separations by ultrafiltration); Curt Breneman (materials genemics for structure property predictions) RPI; Chris Bystroff (Protein computational design) RPI; Professor Cynthia Collins (microbial communities, cell-cell communication); Stephen Cramer (proteinsurface interactions, molecular bioprocessing and bioseparations) RPI; James Crivello Cramer (chemical polymer synthetic routes applied to biobased systems) RPI; Professor Michael Cunningham (Biobased surfmers for emulsion polymerization systems; Queens University, Canada); Peter Dinolfo (Design and synthesis of supramolecular coordination compounds, electrochemisty and spectroscopy of inorganic compounds) RPI; Jon Dordick (Nanobiotechnology: application of biomolecule-nanoparticle composite materials with tailored structure and function); Philippe Dubois (reactive processing, biobased materials) UMons, Belgium; Richard Gross (Biocatalysis and polymer chemistry) RPI; Mariah Hahn (elucidating cell-biomaterial interactions so as to rationally guide bone and vascular regeneration) RPI; Amir Hirsa (fluid mechanics and interfacial technology) RPI; Professor George John (self assembly, biosurfactants, soft materials) City College at CUNY); Professor Robert J. Linhardt(glyco-chemistry and biology, heparin bioengineering) RPI; City College at CUNY); Professor James Moore (use of biobased building blocks for polymer synthesis) RPI; City College at CUNY); Ravi Kane (interaction between proteins and nanostructures; non-fouling surfaces) RPI; Nikhil Koratkar (Nanobiotechnology: application of nanofibers in smart materials and membrane technologies) RPI; Professor Alan Lyons (printing technologies, CUNY Staten Island); George Makhatadze (Rational design of proteins for thermostability) RPI; Mattheos Koffas (metabolic engineering of unicellular organisms) RPI; Professor Michael Meier (metathesis chemistry on fatty acids and other biobased materials) Karlsruhe Institute of Technology (KIT), Germany; Ganpati Ramanath (nanostructured materials and interfaces for materials discovery and design) RPI; Chang Ryu(Biobased materials, sustainable polymer chemistry, rheology) RPI; Professor Maristella Scandola (Solid-state material properties, fiber electrospinning) University of Bologna, Italy); Linda S. Schadler (properties and morphology of polymer nanocomposites) RPI.

Benefits of Membership

TIndustrial partners are offered the opportunity to leverage the cost of a small percentage of one researcher to gain access to a network of 22 Senior Scientists from Academia and National Labs that work with over 60 Ph.D students. In response to Center member needs/interests, research teams are assembled from the Center network and to perform research projects. Members have the opportunity to become ‘true partners’ in the process of problem solving and discovery. Since different models fit different problems and organizations, Members can define their level of involvement in projects. This ranges from visits to our laboratories, regular teleconferences to quarterly progress reports. The following outlines the benefit of Center membership: 

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  • Leverage the cost of a small percentage of one researcher into the power of 21 Senior Scientists from Academia and National Labs that work with over 60 Ph.D. students.

  • Annually renewable membership allowing you the flexibility to opt in or out as needed. 

  • Cost-effective access to a portfolio of research projects and a network of researchers with an extraordinary breadth of expertise. 

  • Use 60% of your contribution to support a specific research that is kept confidential from other members. Prioritize the use of the remaining 40 % the membership fee that is pooled with other member dollars to address research challenges of mutual interest to members. 

  • Status as a graduated NSF Industrial-Research Center has resulted in a low overhead rate (10%, guaranteed through September 2016). 

  • Rapid information transfer through frequent reports, cost-effect tele- or video-conferencing.

  • On-site learning of experimental methods. 

  • Review meetings every six months where formal presentations are given to discuss accomplishments and challenges and for one-on-one meetings between the Members and Center researchers.

  • Get to know highly trained potential future employees.

  • Access to results from other federally funded projects.

  • Access to state-of-the art core facilities (see below).

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Some benefits to members are more subtle but provide powerful arguments to management for participation. For example, Center research may save Members from investing in similar projects that, if performed in house, would be much more costly. Also, by participation, Members can rapidly target promising new technologies for in-house investment. 

INDUSTRIAL MEMBERS:

Since the Centers inception in April 2000, members have included BASF, Covidien, DSM, Evonik, FMC, PepsiCo, Novozymes, Genencor, W.R. Grace, Johnson & Johnson, Esteé Lauder, Cognis, Sherwin Williams, Grain Processing Company, EcoSynthetic’s, DNA 2.0 and Nalco. 

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The CBBM will be housed within the Center for Biotechnology and Interdisciplinary Studies Building (CBIS), which supports several state-of-the-art Research Cores that are available to all Rensselaer faculty, staff and students and also to external academic and industrial collaborators and researchers. Core facilities are summarized below: 

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  • The Analytical Biochemistry & Nanobiotechnology Research Core includes a Biacore 3000 (surface plasmon resonance) system, Differential Scanning Calorimeter, a fluorimeter, a small angle X-ray scattering system, a circular dichroism spectrophotometer, a UV-vis spectrophotometer, a wide-angle X-ray scattering system and an array of dynamic and static light scattering instruments 

  • The BioImaging Research Core features a Bruker 600 MHz Wide-Bore Solid-State 14T NMR and Multichannel Heteronuclear Microimaging Spectrometer and a Bruker Pharmascan 16cm 7T Horizontal MRI / MRS system. The Core also integrates equipment from other Corers in imaging studies, including the CT Scanner and the MALDITOF/TOF spectrometer. 

  • The BioResearch/Animal Research Core houses multiple research rodent colonies, including transgenic lines, a Zebrafish research facility and a Pharmascan Small Animal Imaging Horizontal MRI/ MRS suite. 

  • The Cell & Molecular Biology Core laboratories offer standard tissue culture facilities, a BD FACS sorter and analyzer, an Amaxa Nucleofector 96-well Shuttle System, a GE Typhoon Trio+ Imaging system, multiple thermal cyclers and molecular analysis equipment and an RTPCR system. 

  • The Microbiology and Fermentation Core includes two 40 liter BioFlo fermentors, a 20 liter BioFlo fermentor, multiple centrifuges and ultracentrifuges, a French Press and an analytical ltracentrifuge. 

  • The Microscopy Core offers multiple Zeiss confocal microscopes (equipped with lasers, multiphoton, and optical tweezermolecular capture accessories), an Asylum Atomic Force microscope equipped with TIRF accessories and a high resolution Micro CT in vivo scanner. 

  • The Nuclear Magnetic Resonance Core (NMR) houses an 800 MHz unit, a pair of 600 MHz spectrometers (solution and wide bore solid phase equipped with small animal imaging capabilities) and a LINUX computation cluster. 

  • The Proteomics Research Facility offers a dedicated sample preparation and HPLC laboratory, a Bruker MALDI-TOF/TOF mass spectrometer, a Thermo LTQ-Orbitrap mass spectrometer and a Thermo TSQ mass spectrometer.

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