Advances in protein engineering, the advent of new chemistries and custom-made biocatalysis are leading to broader industrial enzyme across a range of industries, including pharma, fine chemicals and agriculture. Coupled with advances in systems and synthetic
biology, the opportunities to create sustainable, scalable and cost-effective chemical production are greater than ever.
Cambridge Healthtech Institute’s Second Annual Biocatalysis and Bio-Based Chemical Production conference tackles the latest technical and industrial advances in biocatalysis, enzyme engineering and synthetic biology, with dedicated
sessions on new chemistries, protein engineering and novel applications of enzymes across a range of industries.
Final Agenda
TUESDAY, JANUARY 9
1:00 pm Registration
1:30 Refreshment Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Opening Remarks
David Rozzell, Ph.D., Senior Vice President, Biocatalysis, Provivi
2:05 The Discovery of a New Enzyme ‘Reductive Aminase’
Nicholas Turner, Ph.D., Professor, Chemical Biology, University of Manchester
The reductive aminase from Aspergillus oryzae (AspRedAm) is an NADP(H)-dependent oxidoreductase that has been shown to catalyse the enantioselective reductive coupling of a remarkably broad set of ketones and aldehydes with different amines, ranging
from primary/secondary amines to ammonia, in up to >98% conversion and with >98% enantiomeric excess. The AspRedAm wild-type biocatalyst has been applied to reductive amination reactions on a preparative-scale, displaying total turnover
numbers up to 32,000.
2:45 From Novel Enzymes to de novo Pathways and Designer Strains
Alexandre Zanghellini, Ph.D., CEO, Arzeda
Our ability to design cell factories to produce valuable chemicals requires the “recombination” not only of existing but also designer enzymes into novel metabolic pathways to achieve entirely new metabolic function. To this end, Arzeda
is developing high-throughput computational methodologies to exploit natural enzyme latent catalytic promiscuity to rapidly design new catalysts. Successful applications of this approach will be presented.
3:15 Genomic Mining of Aldehyde Deformylating Oxygenates Defines Structural Features that Enable Engineering of Function
Justin Siegel, Ph.D., Assistant Professor, Biochemistry & Molecular Medicine, UC
Davis Genome Center
I will discuss the combination of genomic mining, structural biology, and machine learning to determine the structural features that enable soluble aldehyde deformylating oxygenase (ADO) activity. These features were then used to introduce ADO’s
activity into the small subunit of ribonucleotide reducatase.
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing
4:30 Bioinformatics and Machine Learning Methods to Accelerate Enzyme Engineering
James Lalonde, Ph.D., Senior Vice President, R&D, Codexis
Enzyme engineering has benefited from technological advances in the design, testing, and analysis of variant libraries. Molecular modeling methods inform library design, while automation (particularly for sequencing) accelerates testing, and machine
learning algorithms facilitate elucidation of complex structure-function relationships. Integration of such advances will be presented, along with case studies highlighting efficient enzymatic synthesis of active pharmaceutical ingredients.
5:00 PANEL SESSION
David Rozzell, Ph.D., Senior Vice President, Biocatalysis, Provivi
Nicholas Turner, Ph.D., Professor, Chemical Biology, University of Manchester
Alexandre Zanghellini, Ph.D., CEO, Arzeda
James Lalonde, Ph.D., Senior Vice President, R&D, Codexis
Justin Siegel, Ph.D., Assistant Professor, Biochemistry & Molecular Medicine, UC Davis Genome Center
5:30 Close of Day
5:30 - 5:45 Short Course Registration
5:45 - 8:45 Dinner Short Courses*
* Separate registration required
WEDNESDAY, JANUARY 10
8:00 am Registration and Morning Coffee
8:30 Chairperson’s Remarks
David Weiner, Ph.D., Vice President, Technology & Product Development, BASF Enzymes, LLC
8:35 Accelerating the Application of Biocatalysis for Drug Discovery and Development
Douglas Fuerst, Ph.D., Director, GSK Fellow, Advanced Manufacturing Technologies,
GlaxoSmithKline
Advances in biocatalysis and directed evolution are increasing the number of opportunities to apply enzymes and cells in the synthesis of pharmaceutical compounds. This presentation will describe the approach being advanced at GlaxoSmithKline
across both drug discovery and development highlighted with several relevant case studies.
9:05 Biocatalysis: An Enabling Technology for Rapid Chemical Process Development
Jacob Janey, Ph.D., Associate Director, BMS
Biocatalysis has long been recognized as a key, green chemical technology in the design of robust, efficient manufacturing routes for active pharmaceutical ingredients. It also represents an important tool for the rapid execution of “fit-for-purpose”
campaigns to fund supplies of development compounds’ early clinical studies. This talk will focus on informative case studies from BMS’s Chemical and Synthetics Development organization where bespoke biocatalysts have served
as a critical enabling technology for innovative synthetic route development.
9:35 Using the CodeEvolver® Directed Evolution Platform to Create Improved Enzymes for Molecular Diagnostics
Vesna Mitchell, Ph.D., Principal Scientist, Molecular and Cellular Engineering, Codexis, Inc
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Towards a Synthetic Biology Platform for Natural Product Discovery
Charles Moore, Ph.D., Research Investigator, Novartis
The maturation of DNA sequencing technologies coupled with the rapid emergence of synthetic biology has turned (meta)genome mining into an attractive avenue to acquire novel chemical starting points to facilitate early lead discovery.
We present our experiences from a multi-year effort to design and implement a natural product discovery pipeline based on principles of synthetic biology. This effort has permitted us to understand where bottlenecks reside and potentially
how they could be addressed going forward.
11:20 Enzyme Engineering for Regioselective Hydroxylation in a Whole Cell Environment
Toni Lee, Ph.D., Senior Scientist, Biocatalysis, Provivi
Membrane-bound enzymes present unique challenges to protein engineers. We are currently generating (Z)-11-hexadecenol from the alkene using an oleaginous cell catalyst expressing membrane-anchored P450 alkane or fatty acid hydroxylases.
Using a medium-throughput whole-cell screen, we detected hydroxylase homologs or single point mutants with improved regioselectivity for hydroxylating the desired terminus of the alkene. These findings have application to the production
of lepidopteran sex pheromones for use in agricultural pest control.
11:50 The Potential of Biocatalysis for the Synthesis of Small Drugs: Exploiting the Promiscuity of Nucleoside and Nucleotide Phosphorylases
Peter Neubauer, Ph.D., Professor, Department of Bioprocess Technology,
Institute of Biotechnology, Technische Universität Berlin
We develped a broad portfolio of recombinantly expressed thermophilic enzymes with wide substrate promiscuity by novel efficient parallel expression and purification strategies. They are efficient in the synthesis of a wide range of halogenated
nucleosides by one-pot transglycosylation reactions. Also, we established an enzymatic phosphorylation cascade from nucleosides to nucleotides. These tools provide a solid basis for the efficient synthesis of a wide range of novel
substances.
12:20 pm Enjoy Lunch on Your Own
2:00 Chairperson’s Remarks
Yoram Barak, Ph.D., Biosciences Innovation Manager, BASF Enzymes, LLC
2:05 Genome-Scale Engineering: A New Frontier in Metabolic Engineering
Huiman Zhao, Ph.D., Departments of Chemical and Biomolecular Engineering, Chemistry,
and Biochemistry, Bioengineering, Institute for Genomic Biology, and Center for Biophysics and Computational Biology, University of Illinois
Advances in reading, writing and editing genomes have greatly expanded our ability to reprogram biological systems at the resolution of a single nucleotide and on the scale of a whole genome. In this talk, I will highlight our recent work
in the development of new molecular parts and tools for genome-scale engineering and our attempt in automating the design, build and test cycle for strain development.
2:35 Engineering Cofactor Selectivity: Some New Ideas for an Old Problem
Scott Banta, Ph.D., Professor, Chemical Engineering, Columbia University
Engineering cofactor selectivity in dehydrogenases has been an important engineering goal for more than 25 years. We have been engineering just about every aspect of the NAD(H)-dependent thermostable alcohol dehydrogenase D (AdhD) from
Pyrococcus furiosus. I will discuss recent insights into the engineering of the cofactor selectivity of this enzyme, including the introduction of an intrinsically disordered peptide into the active site to tune cofactor selectivity
by calcium addition.
3:05 Refreshment Break in the Exhibit Hall with Poster Viewing
4:00 Bringing Some Structure to Biocatalysis - Designing Genetically Programmable Biocatalytic Systems
Stefan Lutz, Ph.D., Professor and Department Chair, Department of Chemistry,
Emory University
Protein-based nanocompartments represent robust carrier matrices for the assembly of artificial biocatalytic nanoreactors. Challenges related to ineffective permeability of metabolites due to small pores in the protein shell and lacking
exterior surface functionality are addressed through protein engineering, enabling the creation of tailored carriers that can serve as highly versatile scaffold with excellent control over spatial organization of (bio)catalysts.
4:30 Combining Genome-Scale Modeling and Adaptive Laboratory Evolution to Optimize Enzymes and Whole Cells
Adam Feist, Ph.D., Project Scientist, Systems Biology Research Group, University
of California
Constraint-based modeling is a predictive approach which can be utilized to drive metabolic engineering through simulating strain designs and integrating omics measurements. Adaptive laboratory evolution is a powerful experimental
technique that, unlike rational engineering, is conducted without a priori knowledge on how beneficial traits would arise and therefore can result in unintuitive biological mechanisms. These two technologies can be combined
to predict and acquire strains with beneficial industrial biotechnology capabilities.
5:00 Presentation to be confirmed
5:30 - 6:45 Networking Reception in the Exhibit Hall with Poster Viewing
6:45 Close of Biocatalysis and Bio-Based Chemical Production Conference