Cascade Bio

With summer in full swing in the Southern Hemisphere, it is time to shine light on another enzyme from the southern pole. Our January Enzyme of the Month is Candida Antarctica Lipase A (CALA). Last January, we covered CALB, its more popular cousin enzyme, but CALA is worth discussing as well. 🧈 Lipases are enzymes that break down triglycerides (fat) and catalyze a number of esterification reactions. They have industrial relevance in food, specialty chemicals, pharmaceuticals, and clean energy, and they offer a more sustainable alternative to traditional chemical manufacturing methods. 🤝 The yeast candida antarctica, like most living things, has multiple lipases that act in different conditions and on different types of molecules. CALA has better temperature tolerance than CALB and can act on a broader range of molecules. We'll explore the differences in its structure and functionality in the coming weeks. 🧬 CALA is an interesting and valuable enzyme for biocatalysis and beyond, and we are looking forward to sharing more with you over the course of this month. #Biocatalysis #Lipases #Sustainability #Enzymes #CascadeBio

🌲 Pinene synthase is the enzyme responsible for building the bridge of the molecules α-pinene and β-pinene, two of the most abundant terpenes in coniferous plants. These compounds contribute to the distinctive pine aroma we associate with Christmas trees. But beyond their scent, pinene synthase operates through a fascinating mechanism that is a great example of enzyme catalysis in action. 🔬 The active site of pinene synthase is finely tuned to bind geranyl diphosphate (GPP), positioning it perfectly for the cyclization reaction. The enzyme facilitates this reaction by stabilizing the carbocation intermediate, a crucial step in the conversion of GPP to pinene. The specific architecture of the active site, with its hydrophobic and electrostatic interactions, ensures the proper orientation of GPP, allowing for the efficient formation of the bicyclic structure of pinene. 🔧 Pinene synthase catalyzes the conversion of GPP to an allylic cation intermediate, which undergoes a series of intramolecular cyclizations to form the pinene products. The first cyclization occurs when the carbocation intermediate attacks a double bond, forming a cyclohexane ring. The resulting product undergoes a second cyclization to complete the bicyclic structure. The reaction mechanism relies heavily on the enzyme's ability to stabilize these charged intermediates through the electrostatic environment of the active site, facilitating the formation of a specific set of products. Not only that, but the enzyme’s active site also controls the ratio of α-pinene to β-pinene. This is achieved through subtle conformational changes within the enzyme's structure, which influence the direction of the final cyclization step. The enzyme’s ability to balance the production of these two products is an example of how enzymes can exhibit fine control over their catalytic outputs, tailoring the reaction to the needs of the organism. 🌟 From its active site architecture to its intricate mechanism and product specificity, our December Enzyme of the Month pinene synthase is the perfect example of how nature has evolved highly specialized enzymes to produce the terpenes that are crucial for plant metabolism and ecology. #EnzymaticFuture #CascadeBio #Biochemistry #EnzymeMechanism #PineneSynthase #Terpenes #MolecularBiology #Biotech #Biocatalysis

As Cascade Bio enters its third year, both my co-founder James Weltz and I received a gift from our investor Spacecadet. I guess startup life is transforming us as we continue to empower enzymes to change how molecules are made. #enzymes #cascadebio #biocatalysis

🌲 When you smell the crisp, fresh scent of pine trees, you're experiencing the handiwork of pinene synthase. But beyond evoking holiday nostalgia, our December Enzyme of the Month is revolutionizing renewable energy, pharmaceuticals, and even the fragrance industry. Let’s dive in: 🛢️ Pinene synthase is a game-changer in biofuel development for jet fuel alternatives. Unlike fossil-derived kerosene, pinene offers a comparable energy density with a fraction of the carbon footprint. The enzyme catalyzes the formation of α-pinene and β-pinene from geranyl pyrophosphate, yielding hydrocarbons that can be polymerized into high-performance fuels. Unlike chemical synthesis, which requires harsh conditions and petroleum-based inputs, enzymatic production is cleaner and scalable. Researchers are engineering pinene synthase to enhance substrate affinity and turnover rates, further optimizing yields and making renewable aviation fuels economically competitive. 💊 Pinene synthase is also unlocking novel pathways for producing biologically active terpenes. α-Pinene and its derivatives, for instance, are potent anti-inflammatory agents that inhibit cyclooxygenase (COX) pathways, a key target in pain management and inflammatory diseases. By leveraging engineered variants of pinene synthase, we can selectively produce enantiomerically pure pinene, which is critical for pharmacological efficacy. This enzymatic method circumvents the stereochemical challenges of chemical synthesis and eliminates the need for large-scale harvesting of plant material. 🖌️ Traditional extraction of pinene from pine trees is resource-intensive, requiring significant land and water use. The bio-based production approach not only enhances sustainability but also allows for the customization of terpene blends to meet market demands for the complex fragrances and flavor profiles used in many consumer products - especially this time of year. ✨ Pinene synthase provides yet another case study on how enzymes can outperform traditional chemical processes by offering specificity, efficiency, and environmental sustainability. Its applications across energy, medicine, and consumer goods showcase the growing potential of biomanufacturing to tackle challenges that conventional methods can’t address, all while paving the way for a greener future. #EnzymaticFuture #CascadeBio #EnzymeOfTheMonth #Biochemistry #IndustrialBiotech #RenewableEnergy #PharmaceuticalInnovation #GreenChemistry #Biocatalysis

🎄 The festive scent of pine trees is one of December's unmistakable hallmarks. Behind the scent is an enzyme that deserves its moment in the spotlight: pinene synthase, our December Enzyme of the Month. Beyond its connection to the season, pinene synthase plays a vital role in plant defense and has exciting implications in sustainable industrial applications such as biofuels. Let’s dive in: 🧬 Pinene synthase is a terpene synthase enzyme responsible for converting geranyl pyrophosphate (GPP) into the two isomeric forms of pinene: alpha- and beta-pinene. The enzyme performs a cyclization reaction, creating a bridge spanning the six-membered ring of GPP to create a bicyclic compound. This reaction is a crucial step in the secondary metabolism of conifers and other plants, as it produces compounds essential for ecological defense, like insect and pathogen deterrents. The enzyme’s stereospecific catalytic activity ensures the generation of these volatile monoterpenes, which act as deterrents to herbivores and pathogens while simultaneously attracting pollinators and beneficial organisms. ⚡ Pinene synthase has significant industrial potential, particularly in the production of biofuels. The pinenes it synthesizes are precursors to high-energy-density hydrocarbons that can be used in aviation fuels, offering a renewable alternative to fossil fuels. Additionally, the enzyme’s catalytic properties can be harnessed in synthetic biology to engineer microbial systems for large-scale production of pinenes. Beyond biofuels, these compounds have applications in pharmaceuticals, fragrances, and environmentally friendly solvents, showcasing the enzyme's versatility and industrial promise. In fact, Pinene synthase has shown potential in cancer research, as the compounds it produces can exhibit cytotoxic properties against certain cancer cell lines. 🎁 Pinene synthase is more than the festive fragrance of its product. From its role in plant defense to its transformative potential in biofuels, this enzyme bridges the natural and industrial worlds. As we celebrate the season, it’s worth appreciating the biochemical marvels that make nature—and innovation—possible. #EnzymaticFuture #CascadeBio #Biochemistry #EnzymeOfTheMonth #PineneSynthase #Biofuels #Sustainability

Thanks Wiz 👨🚀 ‏‏‎ ‎for the awesome holiday gift! What we call enzyme cascades at Cascade Bio, you call forging new pathways in the fabric of life itself. Well said.

Welcome Khloe Kleinstuber to the Cascade team! Our newest team member is making her return to her home state of Colorado after a brief stint in Oregon where she got her masters in chemistry.

I will be attending the 4th annual Applied Biocatalysis & Enzyme Engineering Summit in Philadelphia next week. I am looking forward to learning more about the cutting edge of biocatalysis from an excellent list of speakers and sharing how Cascade Bio reduces the cost and increases the utility of biocatalysts with our Body Armor for Enzymes technology. If you're attending or in the area, it would be great to connect!

Happy Thanksgiving from Cascade. We appreciate your enthusiasm for enzymes and learning more about the catalysts that build the natural world. Now back to our regular programing with the final post on our November Enzyme of the Month tryptophan synthase. 🧬 🧑🍳 For the final post, we’ll look closely at the mechanism of tryptophan synthase and how it cooks up this critical amino acid. This enzyme has multiple parts and does two different reactions. The α-subunit of the enzyme catalyzes the cleavage of indole-3-glycerol phosphate (IGP) into indole and d-glyceraldehyde-3-phosphate (G3P). The indole produced in the α-reaction is then channeled through a 25 Å tunnel to the β-active site. 🍽️ The β-subunit of the enzyme catalyzes the reaction of indole with l-serine to produce l-tryptophan, requiring a pyridoxal phosphate (PLP) cofactor. A lysine in the active site of both subunits does a lot of the heavy lifting facilitating the interaction between the intermediates. Here at Cascade, we look to enable multiple enzymatic steps easily in a single reactor for more sustainable chemical production. We are thankful for proteins like tryptophan synthase where nature already puts two reactions into a single enzyme. Hope everyone has a great day! 🦃

🧬 For our third post on our November Enzyme of the Month tryptophan synthase, we will explore recent research and innovations done on the enzyme enabled by advances in biotechnology and AI. 💊 Work from Caltech in the late 2010s on tryptophan synthase led to the evolution of the enzyme to synthesize non-canonical amino acids (ncAAs) as well as the founding of the company Aralez Bio. These ncAAs not only expand the repertoire of amino acids available for biochemical and pharmaceutical applications but also pave the way for novel protein engineering and therapeutic discoveries. This is possible because ncAAs expand the building blocks nature uses for proteins beyond the 20 canonical amino acids. 🕝 Study of tryptophan synthase has also helped us wind back the clock on understanding life on Earth. Ancestral reconstruction of this enzyme across life indicates that the ancient tryptophan synthase had all 19 other amino acids besides tryptophan, suggesting it was the 20th and final amino acid synthesized by our ancient ancestors billions of years ago. Even though less common than other amino acids, tryptophan is critical for structural diversity of proteins and was probably a huge advantage for the ancient life that used it. Whether pushing forward proteins and therapeutics of the future or enabling the complexity of life billions of years ago, tryptophan synthase has stayed busy. Stay tuned next week for the final post on our November Enzyme of the Month. 🗓️ #enzymes #tryptophansynthase #LUCA #biocatalysis