Enzymes transforming molecules with glowing coenzymes.

Enzyme Engineering: Can We Make Enzymes Work Better for Us?

Reese Marlowe in Science & Nature November 2025 • 3 min read.

"Unlocking the potential of oxidoreductases through protein engineering for improved specificity and efficiency."

Enzymes are nature's catalysts, speeding up chemical reactions with remarkable precision. Among these, oxidoreductases are a vast group, playing a critical role in transferring electrons from one molecule to another. These enzymes are indispensable in various industrial applications, enabling processes that are environmentally friendly and highly selective.

Many oxidoreductases rely on nicotinamide adenine dinucleotide (NAD) or its phosphorylated form, NADP, as coenzymes. These coenzymes aren't just helpers; they're essential for the enzyme to function. However, NAD and NADP have different properties—stability, cost, and availability—making the enzyme's preference for one over the other a significant factor in practical applications.

Scientists are exploring ways to manipulate enzyme coenzyme specificity through protein engineering. This involves modifying the enzyme's structure to favor one coenzyme over the other, aiming to enhance its performance in specific industrial processes.

What is Coenzyme Specificity and Why Does it Matter?

Enzymes transforming molecules with glowing coenzymes.

Coenzyme specificity refers to an enzyme's preference for either NAD or NADP. Enzymes involved in building molecules (anabolic processes) often prefer NADP, while those breaking down molecules (catabolic processes) typically prefer NAD. This preference is dictated by the enzyme's structure, which creates a binding pocket tailored to fit either NAD or NADP.

Modifying this specificity can have several benefits:

Cost Reduction: NAD is generally more affordable than NADP, making it desirable for industrial processes.
Increased Stability: NAD often exhibits greater stability than NADP, which can be advantageous in certain applications.
Improved Efficiency: Tailoring the enzyme to use the more readily available coenzyme can streamline metabolic pathways and enhance overall process efficiency.

Researchers are employing various strategies to alter coenzyme specificity, including site-directed mutagenesis, saturation mutagenesis, and loop exchange. These techniques aim to modify the enzyme's binding pocket to better accommodate the desired coenzyme.

Challenges and Future Directions in Enzyme Engineering

While altering coenzyme specificity holds immense promise, it's not without its challenges. One major hurdle is maintaining or even improving the enzyme's catalytic activity after modification. Often, changes that favor the desired coenzyme can compromise the enzyme's ability to perform its primary function efficiently. Computational tools and algorithms are becoming increasingly valuable in guiding protein engineering efforts. These tools can help predict the effects of mutations on enzyme structure and function, streamlining the design process. As technology advances, the ability to tailor enzymes for specific industrial applications will become more precise, revolutionizing various sectors.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3389/fmicb.2018.00194, Alternate LINK

Title: Protein Engineering For Nicotinamide Coenzyme Specificity In Oxidoreductases: Attempts And Challenges

Subject: Microbiology (medical)

Journal: Frontiers in Microbiology

Publisher: Frontiers Media SA

Authors: Andrea M. Chánique, Loreto P. Parra

Published: 2018-02-14

Everything You Need To Know

What are oxidoreductases, and why are they significant in industrial applications?

Oxidoreductases are a group of enzymes that catalyze the transfer of electrons from one molecule to another. This makes them crucial in a variety of industrial applications. They're favored because the processes are environmentally friendly and highly selective, providing efficiency and precision in chemical reactions. These enzymes are used to perform reactions, like in pharmaceuticals and biofuels production, making them indispensable across various industrial applications.

How does coenzyme specificity influence the efficiency of enzymes such as oxidoreductases?

Coenzyme specificity refers to an enzyme's preference for either NAD or NADP. The selection matters a lot. Enzymes like oxidoreductases depend on coenzymes such as NAD and NADP to function. Modifying this specificity can result in cost reduction and improved efficiency. The enzyme's structure creates a binding pocket tailored to fit either NAD or NADP. For example, tailoring the enzyme to use the more readily available coenzyme can streamline metabolic pathways and enhance overall process efficiency.

What are the primary differences between NAD and NADP, and how do these differences affect enzyme engineering?

NAD and NADP are both coenzymes, but they have different properties, impacting their use in enzyme engineering. NAD is generally more affordable and often exhibits greater stability than NADP. Enzymes involved in anabolic processes often prefer NADP, while those breaking down molecules (catabolic processes) typically prefer NAD. Scientists modify the enzyme's structure to favor one coenzyme over the other, aiming to enhance performance in industrial processes. This approach allows researchers to select for stability, cost, and availability by manipulating the enzyme's affinity for these coenzymes.

What techniques are scientists using to modify enzyme coenzyme specificity, and what are the potential benefits?

Scientists use various strategies to alter coenzyme specificity, including site-directed mutagenesis, saturation mutagenesis, and loop exchange. These techniques modify the enzyme's binding pocket to better accommodate the desired coenzyme. The potential benefits include cost reduction, increased stability, and improved efficiency. By adjusting an enzyme's preference for either NAD or NADP, researchers can make industrial processes more economical and effective, utilizing more stable and accessible coenzymes.

What are the major challenges in enzyme engineering, and how are computational tools helping to overcome these hurdles?

One major challenge in enzyme engineering is maintaining or improving catalytic activity after modification. Changes that favor the desired coenzyme can sometimes compromise the enzyme's efficiency. Computational tools and algorithms are becoming increasingly valuable in guiding protein engineering efforts. These tools help predict the effects of mutations on enzyme structure and function, streamlining the design process. Advances in technology enable more precise tailoring of enzymes for specific industrial applications, potentially revolutionizing multiple sectors.