Cascade Bio

It was an absolute blast, thanks Daniel Goodwin for the opportunity to nerd out and share our vision for an enzymatic future.

Throughout March, we've explored the history and industrial impact of amylase—now let’s dive into how this powerhouse enzyme works. ?? ?? ??????????????: ?? ?????????????????? ?????????????????? Amylase belongs to the glycoside hydrolase family—enzymes that break glycosidic bonds, the links between sugars in starch. Unlike serine hydrolases such as previous lipase enzymes of the month, amylase doesn’t rely on a reactive serine. Instead, it uses acid-base catalysis, where amino acids in the active site donate and accept protons to break bonds efficiently. ?? ?????? ?????????????????? ??????????????????: ???????????????? ???????? ???????????? Amylases generally follow one of two strategies to cleave starch: 1?? Retaining Mechanism – Uses a two-step, double-displacement reaction where the enzyme briefly forms a covalent intermediate with the starch molecule before hydrolysis. 2?? Inverting Mechanism – A single-step reaction where water directly attacks the bond, assisted by amino acids that help position and activate it. Regardless of the mechanism, precisely placed acidic and basic residues in the active site orchestrate this process, making amylases highly efficient catalysts. ?? ?? ?????????????? ?????? ?????? ???????????? Amylases have specialized active sites tailored to different starch structures: ?? α-Amylase – Randomly cleaves α-1,4 bonds, rapidly breaking starch into shorter fragments. ?? β-Amylase – Works stepwise, removing maltose units from the starch ends. ?? Glucoamylase – Cleaves both α-1,4 and α-1,6 bonds, yielding glucose directly. Each type of amylase is fine-tuned for specific industrial and biological roles. ?? ?? ????????-???????????? ?????????????????????? ???????????????? The glycoside hydrolase mechanism is one of nature’s most widely used catalytic strategies, evolving independently in bacteria, plants, and animals to break down complex carbohydrates. This molecular precision fuels everything from digestion to fermentation to industrial biotechnology. Stay tuned for more enzyme deep dives as we wrap up our focus on our March Enzyme of the Month next week. #EnzymeOfTheMonth #Amylase #Biotech #Biocatalysis #EnzymaticFuture #CascadeBio

Excited to share that Cascade Bio has been selected for Third Derivative's inaugural Industrial Innovation Cohort focused on decarbonizing the chemicals industry. I am looking forward to learning from and growing alongside other innovative startups with similar missions to make molecules in a better way.

From food production to biofuels, our March EOTM amylase is one of the most widely used enzymes in industrial biotechnology. It catalyzes the breakdown of starch into sugars, unlocking efficiency across multiple sectors: ?? ?????????????????– Amylase is a key player in ethanol production, breaking down complex starches into fermentable sugars, making biofuel production more sustainable. ?? ?????????????? & ???????????????????? – The beer and whiskey industries rely on amylase to convert starches in grains into fermentable sugars, ensuring consistent quality and yield. ?? ???????? & ???????????????? – From improving bread texture to producing syrups, amylase enhances food processing efficiency and product quality. ?? ???????????????? & ???????????????????? – Amylase removes starch-based stains and residues, improving fabric processing and enhancing laundry performance. ?? ?????????????????????????????? – Used in digestive enzyme formulations, amylase supports gut health and metabolic processes. ???????????? ?????????????????????? The global amylase market is around $2B today, driven by growing demand in biofuels, food processing, and detergents. With enzymatic solutions replacing traditional chemical processes, industries are prioritizing efficiency, sustainability, and cost-effectiveness—all areas where amylase excels. Amylase is quite the unsung hero of industrial biocatalysis. #Biotechnology #Enzymes #Amylase #IndustrialBiotech #Sustainability #EOTM #Biocatalysis #Biomanufacturing

On Tuesday, the Climate Biotech podcast will be interviewing my co-founder James Weltz. Tuesday also happens to be his birthday. So come join the recording to learn more about Cascade, ask about James's journey and wish him a happy birthday! ?? https://lnkd.in/edU2NH_6

Our March Enzyme of the Month amylases are enzymes that break down starch into sugars, making them essential for everything from brewing beer to baking bread. Found in humans, plants, and microbes, these enzymes have played a hidden but crucial role in human civilization—long before recorded history. ?????? ?? ????????????’?? ???????????? ?????????????? Amylases are everywhere in nature, quietly transforming complex carbohydrates into simple sugars. In?human digestion, amylase in saliva kicks off starch breakdown as soon as you take a bite. In?plants, sprouting grains activate amylases to convert stored starch into sugar, fueling early growth. Even?soil microbes?use amylases to break down plant material, cycling nutrients through ecosystems. Without amylases, nature’s food web—and our diets—would look very different. ?? ?????????????? ???????????????? ?????? ?????????????????? ???? ?????????? Ancient civilizations used malted grains (rich in amylase) to brew beer, make fermented porridges, and bake leavened bread. Used heavily since the dawn of civilization, this enzyme-driven process is still the foundation of many staple foods today. ??????????????? ?????????????? Now, with our advanced understanding of this enzyme and its biochemistry, amylases are now used heavily in diverse industries: ? ?????????????? & ???????????????????? – Convert starches into fermentable sugars for beer and whiskey ?? ? ???????????? – Improve dough texture and extend shelf life ?? ? ???????????????????????????– Make sweet syrups for candies and soft drinks ?? ? ???????????????? & ?????????? – Remove starch coatings for smoother processing ?? ? ???????????????? – Break down plant material for ethanol production ?? ? ???????????????????? – Powerful stain-busting action for starch-based stains ?? This month, we’ll explore the many ways amylases drive industrial innovation—from brewing and baking to detergents, biofuels, and beyond—while also taking a closer look at their role in St. Patrick’s Day favorites like beer and sweet treats. Stay tuned!??? #EnzymeOfTheMonth #Amylase #Biotech #Fermentation #StarchToSugar #Enzymes

We are at the tail end of February, and so it is time for our last post on ?????????????????????????????? ??????????-?????????????????? ?????????????????????????? (??????)—a fascinating enzyme responsible for C-terminal amidation of peptides, a modification that is crucial for biological activity in many signaling molecules. ?????? ???????? ???? ????????? PAM catalyzes a two-step oxidative reaction: 1?? Hydroxylation of the terminal glycine in peptidylglycine substrates, using molecular oxygen and a cofactor. 2?? Oxidative cleavage, which removes glyoxylate and leaves behind the functionally critical α-amide (-CONH?) on the peptide. This seemingly small chemical tweak has big biological implications, stabilizing peptide hormones and neuropeptides for improved receptor binding, bioavailability, and function. ?????????? ???????? ?????? ???? ???????? ????????? While PAM naturally amidates peptide hormones (e.g., vasopressin, oxytocin), its mechanism suggests broader potential: ?? Custom Peptides: Could engineered versions of PAM modify synthetic peptides for therapeutic applications? ?? Biomanufacturing: Harnessing PAM in cell-free or enzymatic pathways could simplify peptide functionalization. Of course, here at Cascade we are big fans of cell-free ?? New Biocatalysts: Understanding PAM’s active site could inform the design of enzymes for other precise post-translational modifications As we wrap up this series, let's thank PAM for all its hard work putting the final touches on a whole range of biorelevant compounds. So long for now! #Enzymes #Biocatalysis #PeptideEngineering #SyntheticBiology #PAM #Biomanufacturing #CascadeBio

Last time, we introduced ?????????????????????????????? ??????????-?????????????????? ?????????????????????????? (??????)—the enzyme responsible for the final step in making bioactive peptides like oxytocin aka the "love molecule". But why is this modification so important and why is this enzyme critical for biology? ???????? ?????? ????????????????? Peptides are short chains of amino acids that act as molecular messengers, controlling everything from metabolism to brain function. Many peptide hormones—like GLP-1 for regulating blood sugar or calcitonin for regulating calcium levels—require precise chemical structures to work effectively. Proteins are also chains of amino acids, and peptides can be thought of as much shorter versions of them. Both are synthesized in similar ways, following the central dogma of molecular biology: DNA is transcribed into RNA, which is then translated into an amino acid chain. However, peptides are often produced as fragments of larger proteins or through specialized biosynthetic pathways, rather than always following the same processing steps as full-length proteins. ?? ?????? ???? ???????? ???????? ??????? As we discussed last time, PAM performs C-terminal amidation—the addition of an amide (-NH?) group at the peptide’s tail. This is needed because the carboxyl (-COOH) group at the C-terminal can be reactive, potentially altering the stability, binding properties, and biological activity of the peptide. C-terminal amidation neutralizes this charge, helping the peptide maintain its specific structure and interactions with target proteins. ??? So as we celebrate Valentine’s Day, let’s show ?????????????????????????????? ??????????-?????????????????? ?????????????????????????? some love and appreciate all the catalyzing it does behind the scenes—helping bring bioactive peptides like oxytocin to life and making human connection, trust, and affection possible at the molecular level ?? #EnzymeOfTheMonth #PAM #Biocatalysis #BiotechInnovation #ValentinesDay #Peptides

For February's Enzyme of the Month, we present ?????????????????????????????? ??????????-?????????????????? ?????????????????????????? (??????) – The Final Touch for Bioactive Peptides. With?Valentine’s Day around the corner, it’s the perfect time to highlight an enzyme that plays a key role in the biosynthesis of?oxytocin—the “love molecule”. ?? ???????? ???? ??????? Peptidylglycine alpha-amidating monooxygenase (PAM) is an enzyme that?catalyzes the final step?in the production of many bioactive peptides, including?oxytocin, vasopressin, and neuropeptides critical for hormone regulation and neurotransmission. It ensures peptides are fully functional by adding a C-terminal amide (-NH?) group—a modification essential for their biological activity. ?? ? ?????? ???? ???????? ??????????????????? C-terminal amidation is crucial for many?pharmaceutical peptides. PAM-driven biosynthesis is a potential?sustainable alternative to chemical amidation, which often relies on harsh conditions and reagents. This could enhance the efficiency of producing?therapeutic peptides?like calcitonin (osteoporosis treatment) and GLP-1 (diabetes therapy). ?? ???????????? ???????????????? & ???????????????????????? PAM isn’t just about oxytocin—it plays a role in?hormone regulation, neurobiology, and even venom bioactivity in marine organisms! Ongoing research explores its use in?biocatalysis for peptide drug development, offering a?greener, enzyme-driven approach?to making bioactive peptides. Without PAM, our bodies couldn’t fully activate oxytocin—meaning this enzyme might just be responsible for some of those warm, fuzzy Valentine’s Day feelings! #EnzymeOfTheMonth #Biocatalysis #Oxytocin #ValentinesDay #Biomanufacturing #PeptideTherapeutics

As we have discussed throughout January, Candida antarctica lipase A (CALA) is a powerful biocatalyst. However, in industry, Candida antarctica lipase B (CALB) is the money maker while our January Enzyme of the Month CALA remains more in the lab. Here's why: ?? ???????????????????? ???????????????????????? & ?????????????????? ???? ??????????: CALB has been commercialized for decades, and suppliers have optimized production, supply chains, and cost efficiency. Large-scale fermentation and purification processes for CALB are well-optimized, making it cost-effective. Since fewer companies manufacture CALA, it is less widely available and more expensive for industrial applications. ?? ???????????? ?????????????????????? & ??????????????????????: CALB has a well-defined substrate selectivity, favoring secondary alcohols and esters with high efficiency, making it useful in pharmaceuticals, flavors & fragrances, and biodiesel. While CALA has broader substrate scope, its lower activity and lower selectivity for industrially relevant reactions make it less desirable in specific applications. ?? ???????????????????????????? & ??????????????????????: CALB is easier to immobilize on traditional carriers, making it ideal for repeated batch processes or continuous flow reactions. CALA does not immobilize as efficiently, making it less desirable for industrial reusability. Cascade's tunable immobilization platform solves this problem. ? ?? ???????????????? ??????????????????????????????:?Because CALB has been used extensively for decades, many industrial processes and patents reference CALB-specific conditions. Switching to another enzyme, such as CALA, would require costly process re-optimization, re-validation, and regulatory updates. This creates a lock-in effect, where industries continue using CALB because it is already validated and proven. While CALA has some unique properties, CALB dominates the industry due to its commercial availability, performance, immobilization, and lower risk in process development. Once an enzyme becomes widely used, it benefits from economies of scale and industry standardization, reinforcing its dominance over potential alternatives like CALA. However, scalable immobilization platforms like the one we are building at Cascade will make it easier to onboard new enzymes with better performance for specific transformations.