Transcript Overview of the Flagship Program

Chemical & Pharmaceutical
Engineering
(Begun on July 1, 2006)
PSRC Review of Flagship Program
June 20, 2007
Raj Rajagopalan (Singapore) & Bernhardt L. Trout (MIT)
Program Co-Chairs
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Overview of the Flagship Program
Three thrusts focusing on the Pharmaceutical Industry
• Thrust A: Metabolic Engineering:
Molecular Biotechnology for Engineering
Targeted Biological Pathways
• Thrust B: Chemical Catalysis:
Engineering Catalysts at the Molecular
and Nanometer Scales
• Thrust C: Downstream Processing:
Molecular Engineering for Separation
Technology, Purification, and Formulation
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Overview of the Flagship Program
Principal Professors in Each Thrust
• Thrust A: Metabolic Engineering:
– Saif Khan (NUS) & Li Zhi (NUS)
Greg Stephanopoulos, Too Heng-Phon (NUS)
& Danny Wang (MIT)
• Thrust B: Chemical Catalysis:
– Steve Buchwald (MIT), Saif Khan (NUS), Loh
Teck Peng (NTU) & Mark Saeys (NUS)
• Thrust C: Downstream Processing:
– T Alan Hatton (MIT), Raj Rajagopalan (NUS),
Michael Tam (NTU), Bernhardt Trout (MIT),
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Miranda Yap (BTI, NUS)
Manpower
• 5 Direct PhD students entering in 2006
• 6 Direct PhD students to enter in 2007
(Another is pending)
• 1 Joint Post-Doc (started Feb., 2007)
• 1 Post-Doc at NUS (started in March
2007)
• 7 MIT PhD students started in 2006-2007
• 6 MIT post-docs started in 2006-2007
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Key Accomplishments
•
Thrust A: Metabolic Engineering:
•
Thrust B: Chemical Catalysis:
– Initiated enzymatic synthesis on chiral chemical intermediate and co-factor
regeneration using magnetic nanoclusters. Preliminary results show excellent promise
on this new and novel biocatalysis and co-factor regeneration systems
– Demonstrated taxadiene biosynthesis in Escherichia coli at significant amounts.
Taxadiene is the first, most difficult step in the synthesis of taxol from precursors of the
isoprenoid pathway. (Planning to submit a patent application)
– Developed the state of the art catalyst system for the carbonylation of aryl sulfonates,
including the first system for the carbonylation of aryl mesylates. These (aryl tosylates)
are less reactive than aryl halides and are industrially very desirable precursors to
aromatic amides and esters.
– Set up a working microfluidics facility at NUS; Currently fabricating microreactors for
chemical synthesis.
•
Thrust C: Downstream Processing:
– Demonstrated control of protein mobility selectively using light responsive gels, that
certain liquid crystal mixtures can show chiral selectivity in solubilization of derivatized
amino acids, and that magnetic nanoparticles can be fucntionalized with chiral
selectors.
– Developed initial molecular understanding of synthon growth of target crystals.
– Developed a molecular thermodynamic model to follow aggregation in the presence of
excipients.
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Industrial Interactions and
Anticipated Sponsorships
• Pfizer – verbal commitment, finalizing
contract
• MerLion – verbal commitment, finalizing
scope of work
• A-Bio – project to be defined in 2007
• Other companies with prospective interest
are: Novartis, Merck, Schering-Plough,
and S*Bio
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Other Efforts in Progress
1. “Industry Day” Workshop for Singapore’s pharmaceutical industries
is planned to highlight CPE Program’s research and educational
activities and their relation to Singapore’s needs (e.g., Glaxo)
(This effort will also be used to develop closer interactions with
local pharmaceutical and chemical companies and the CPE Team
in order to continually refine the program needs and goals.)
2. Industrial tours are planned for both DM and DP students to local
industries. One to Glaxo was conducted earlier this year.
3. Career Planning Workshops for the students (to emphasize the
“soft” skills they need) are planned at NUS.
4. Critical Thinking Boot Camp: DP students will be asked to enroll in
the “Critical Thinking Boot Camp”, to be run by ChBE @ NUS, to
learn how to read technical papers, how to develop research
projects and proposals, etc.
5. Presentation Skills Workshop: Students will enroll in Professional
Presentation Skills Workshop run by Prof. Bill Krantz at ChBE @
NUS.
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Personnel Changes
• Prof. Michael Tam (Thrust C) has
resigned from NTU (effective July 1, 2007)
to accept a faculty position in Canada.
• Prof. Neal Chung (Thrust C), who has
strong expertise and industrial
collaborations in the area of membrane
separations for pharmaceuticals, will join
the team in July 2007.
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Goals for Next Year
• Thrust A: Metabolic Engineering:
– Enzymatic synthesis of chiral intermediate will be investigated along with
the regeneration of co-factor analogs. Once these are achieved, patent
disclosure will be filed.
– Optimization of the above pathway for maximum taxadiene production and
initiate the construction of the additional ~10 steps to complete the full
taxol pathway. Also, initiation of the engineering of the amporphadiene
pathway for artemisinin synthesis (antimalaria drug).
• Thrust B: Chemical Catalysis:
– Development of a full understanding of the controlling features in our new
carbonylation system as well as extension to the preparation of other
important functional groups such as carboxylic acids. Also, initiation of
work on the carbonylation of aliphatic substrates (much more challenging
than for aromatic substrates).
• Thrust C: Downstream Processing:
– Application of functionalized magnetic nanoparticles to continuous chiral
separations and continued development of responsive gels for
pharmaceutical separations and purification.
– Preliminary design and operation of ferrofluid-based microfluidic
separation processes.
– Development of rational understanding of selected crystallization
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processes and formulations.
Summary
• Research flourishing: anticipated joint
publications in 2007-2008, potentially
patent disclosures.
• Strong interest for industrial sponsorship.
• Needs: more Direct PhD slots for
industrially funded projects.
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