Conference Day Two

Thursday 7th December 2023

Synopsis

• In the context of API synthesis, the biocatalysis community has long relied on three predominant catalyst classes: lipases, ketoreductases, and transaminases
• While reactions catalyzed by these enzymes can enable amazing new synthetic routes to the desired compounds, numerous additional enzymatic transformations remain that are not as routinely implemented in process chemistry
• Discussing a few enzyme classes that are beginning to see increased use in process chemistry and not only highlight the key transformations catalyzed but also take a deeper dive in to how scalable, robust, and cost-effective processes were developed

Synopsis

• Two improved routes to BIIB091 key tetrahydrobenzoazepine core BIO-1772469 were developed to support tox an d early clinical demands
• The second improved route uses Amine TransAminase (ATA) biocatalysis reaction of N-Boc ketone precursor which was prepared by applying a trifluoroacetamide protecting group for effective azepine ring construction and protecting group swap
• The ATA biocatalysis route was demonstrated at sub kilogram scale and has the potential to become late clinical and commercial route due to its significant improvements in synthetic efficiency, overall yield, and process greenness

Synopsis

Reduction of nitro aromatics to anilines has been one of the essential transformations in the chemical industry. Common practice utilizes highly hazardous materials such as high pressure hydrogen gas, Pd/C, Fe, or Zn, and therefore, present a safety hazard to scale up

In order to safely prepare anilines, an enzyme catalyzed nitro reduction was developed in a productive process with the aid of crucial metal co-catalysts. This reduction process tolerates olefines and aryl halides, which are often not compatible with the conventional methods. We have developed the biocatalytic nitro reduction to access API raw materials

We hope to present the efforts towards API raw material deliveries, process metrics and cost of goods analysis, and future directions based on the metrics analysis

Synopsis

• Meet and connect with your peers in this dedicated networking session 

Synopsis

• Developed a transaminase reaction
• Replace a 3x step reaction with 1, resulting in the efficient removal of acetone
• Overcoming container/reactor challenges going from reaction scale to 115kg

Synopsis

As the enzymatic IP landscape becomes more nuanced and complex, impacting outsourcing Vs in-house enzyme engineering decision-making, use this discussion-based session to gain cross-stakeholder & cross-industry perspectives on:

• With the intellectual property generated by the development of cutting-edge biocatalysis technologies, how is the patenting and the IP landscape evolving and how is this impacting biocatalysis’ adoption and scaling?
• When is it the right time to transition to different catalysts that’s more beneficial from an IP / cost / ease of manufacture route?

Synopsis

• Take this chance to meet the expert speakers, connect with your peers and explore our exhibition booths

Synopsis

• Belzutifan (MK-6482) is an FDA approved HIF-2α inhibitor for the treatment of Von Hippel−Lindau (VHL) disease-associated renal cell carcinoma (RCC). One of the key synthetic steps is an enzymatic benzylic hydroxylation of an indanone
• Removal of protein residue form enzymatic oxidation reaction: Several approaches were studied and final filtration method was developed from filter aids screening to isolate high quality product
• Development of scalable oxidation process: Prior to optimization, hydroxylation reactions required dilute conditions (100 volumes of water) and high enzyme loading (50 wt%) to achieve the target conversion which were unsuitable conditions for a long-term manufacturing process. Process optimization identified 1-Octanol is an optimal additive to address these challenges
• Scaleup challenges and results: The reduction of reaction volumes introduced additional complexity for large scale operation due to low solubility of the reaction components. With understanding of dissolution rate of starting material and mixing parameters, the hydroxylation process using only 25 volumes of water, 7.5 Wt% of enzyme and 3 Vol% 1-octanol was successfully scaled up at multi kg scale

Synopsis

• Preparation of a novel biocatalyst by co-expressing spinach glycolate oxidase and catalase in methylotrophic P. pastoris: Production of pyruvic acid from lactate and scale-up
• Chemo-enzymatic one-pot dynamic resolution of 2-hydroxy acids by glycolate oxidase (GO) expressed in P. pastoris
• Rapid identification and production of drug metabolites using Stabilized Dried Powder (SDP) of microbial human liver

Synopsis

Your final opportunity to enjoy a drink and bite to eat whilst building your connection base with like-minded stakeholders with a common ambition to utilize biocatalysis to see greater efficiency and catalysis selectivity.

Synopsis

By merging visible light photoredox catalysis and biocatalysis, we advanced a novel mode of pyridoxal radical biocatalysis which is both new-to-biology and new-to-chemistry. This synergistic photobiocatalysis strategy allowed us to repurpose pyridoxal enzymes as new radical enzymes, leading to PLP enzymology never encountered in native biochemistry. 

Pyridoxal radical biocatalysis provides access to a range of non-canonical amino acids, including those bearing contiguous stereocenters, with excellent diastereo- and enantiocontrol. Together, advancement in this area provides a general approach to synthesizing non-canonical amino acid building blocks that are otherwise difficult to access in a convergent and protecting-group-free fashion.

This presentation will share a general strategy to develop radical pyridoxal biocatalysis, rapid assembly of diastereo- and enantioenriched non-canonical amino acids, as well as a new approach to access peptide therapeutics when combined with biocatalytic peptide synthesis

Synopsis

• Compare and contrast two case studies: one applying GSK’s enzyme discovery and directed evolution platform to small molecule reductive amination, the other to glycoside hydrolysis of a complex natural product
• Lessons learned in small molecule biocatalysis can successfully be translated to enzymes operating on large molecules
• In both cases, employing a bienzymatic cascade improves the overall process