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Enzymes can replace conventional chemical production methods with more sustainable, precise, and scalable routes of manufacture. Because of this opportunity, we’re seeing increased adoption of biocatalysis across the chemical industry over time.
Enzyme immobilization – binding an enzyme to a resin or other surface – has shown promise as one route to not only stabilize enzymes to extend their functional lifetimes, but also make it easy to integrate them into a new process in a modular fashion by streamlining product isolation. To date, methods for zeroing in on the right combination of enzyme and immobilization method have been limited in their throughput, requiring extensive and expensive tuning and testing.
In collaboration, Ginkgo Bioworks and FabricNano have teamed up to explore how their platforms can be used to tackle this problem and accomplish previously challenging chemical transformations. One particular transformation, Baeyer-Villiger Monooxygenation, attracted our interest for its potential utility in chemical production for both industrial chemicals and advanced pharmaceutical intermediates (APIs). Current chemical approaches for this reaction require hazardous reagents, and the economic utility of biocatalysts for this reaction has been limited by challenges in expressibility and stability, making it an attractive target.
Experts on the Ginkgo team used metagenomic mining to discover candidate Baeyer-Villiger Monooxygenases (BVMOs) that showed activity on a representative chemical substrate, and then produced batches of the two most promising candidates for testing in FabricNano’s high-throughput immobilization plates. FabricNano’s technical experts took these candidates and tested a range of buffer conditions and resin chemistries, to explore the optimal combination of characteristics to maximize enzyme binding, function, and durability at the same time.
Results comparing the lead enzymes easily identified formulations that allowed both high initial activity and sustained performance at the end of four days of incubation, and for quantitative comparison of the lead enzymes against one another. This process led to a substantial, many-fold improvement in performance that would otherwise have taken extensive iterative testing to optimize both immobilization chemistry and enzyme selection at the same time. The highest-performing combinations’ ability to maintain >50% of activity over four days is compatible with industrial biomanufacturing use cases.
Figure: (a) Initial activity of enzymes after first immobilization and then (b) in a fresh reaction after four days. (c) Plotting of the data from use 4 against use 1 shows that a single Predictive Immobilization Plate can readily identify not only those resins that easily immobilize and retain an enzyme but those specific experimental conditions that maintain enzyme function for multiple days. Datapoints closer to the diagonal indicate higher stability enzymes. (d) Plotting stability vs. activity highlights how formulation and identity of enzyme must both be explored together to find the optimal biocatalyst for a given application.
FabricNano is an enzyme immobilization company, using bioinformatics and formulation to optimize the binding of enzymes to rigid materials. FabricNano has developed the Immobilization Engineering™ platform to guide how enzymes bind to solid materials thereby creating biocatalysts. Using highly-specialized datasets and machine learning, FabricNano can use immobilization to boost biocatalyst stability and efficacy, outpacing performance of conventional methods in enzyme engineering.
Biocatalysts are typically constructed of enzyme machinery: proteins that enable and expedite specific chemical reactions. DNA makes RNA, and RNA makes proteins—and that protein can be put to work as an enzyme executing a very specific chemical reaction over and over again. Nothing about an enzyme is alive, genetically modified, or replicating; it’s just the fundamental machinery for how nature makes materials.
That’s how nature uses enzymes—and industry can, too. www.fabricnano.com
Reach out to us at [email protected] and our friends at FabricNano at [email protected] to learn more about how to pair enzyme discovery and immobilization for your process!
