Producing Recombinant Human Prolactin in a Fruit Fly with Future Fields

Producing Recombinant Human Prolactin in a Fruit Fly with Future Fields

Future Fields team during Prolactin product launch 2024

The Future Fields team celebrating the launch of recombinant human prolactin (PRL-Fc). Though this article features four Future Fielders who contributed to making this protein, please note that it was truly a full team effort!

Future Fields’ prolactin: fly by design, powered by people

Future Fields’ Recombinant Human Prolactin, Fc tag (PRL-Fc) is a protein that is close to our hearts. For our co-founders, at one point in the development process, this was literally the case.

PRL-Fc started off as a recombinant protein to support the cellular agriculture industry, specifically companies focused on producing cultivated milk. The original prolactin strain was cloned from the prolactin protein derived from the breast milk of one of our co-founders: Jalene.

We have since switched over to a synthetic sequence for production, which includes a cleavable Fc-tag - something that is unique to the EntoEngine’s ability to create custom proteins with ease - but the genesis of the research and product development was from a Future Fields’ mom.

Future Fields co-founder Jalene

Jalene out on an ice cream date with her daughter, Rose.

“As one of the few non-scientists on our team, it’s not often I get to personally ‘contribute’ to our research and development efforts, so this protein has an extra special place in my heart,” says Jalene. “I am incredibly excited to see our team’s hard work pay off with the launch of this unique product and look forward to seeing its impact on research–especially in areas supporting women and infant health and nutrition.”

Purifying recombinant human prolactin

Purifying this lactogen hormone was no easy task. Prolactin is a tricky protein, as it is sensitive to proteases, has low stability, and degrades quickly. On the production side, this means that the protein can get lost in the purification process. For Paige, one of our Senior Research Scientists on the Protein Biochemistry team, optimizing the purification protocols for PRL-Fc was her personal project.

Future Fields lab chromatography equipment being prepared for protein purification
Women in STEM - Future Fields Senior Research Scientist Paige holding a vial of recombinant human prolactin, Fc tag

Left: Paige preparing chromotagraphy equipment for purification. Right: Paige holding a vial of Future Fields' Recombinant Human Prolactin-Fc.

Finding the right polishing column was one of the more challenging aspects of producing PRL-Fc. Paige used a systematic approach to find the right ion exchanger, column, conductivity, and pH for this protein. As the polishing column is much less specific than a capture column, it could bind to anything with the same type of charge, so fine-tuning the elution to get the right purity was crucial for the purification process.

Utilizing an Fc-tag was a significant benefit in production. Our PRL-Fc carries a human monomeric IgG1 Fc tag at the C-terminus. This simplified our process and improved the detection and scalability of the protein. Currently, we are conducting studies to investigate the effect of tags on stability and shelf-life of our protein.

As it is a human-derived tag, there are no other risks or safety concerns with the tag; if customers prefer an untagged protein, Future Fields offers the option to cleave the tag from the protein.

“Prolactin has a special place in my heart, partly because I worked on it, and partly because of the topics of study that it can be used for,” Paige says. “I’m excited for the applications of prolactin in R&D, like cultivated breast milk and breast cancer research. There is such incredible, impactful research happening around the world and being able to support those findings is so rewarding.”

A sweet finding: glycosylation

Glycosylation is the process of adding sugar molecules to the hormone. It is a modification that affects how the hormone works. Prolactin has a special site where sugar molecules can be attached called the N-glycosylation site, which is located at the Asparagine (N) at position 31. When PRL is glycosylated, it doesn't stick to receptors as well, but it lasts longer in the body compared to the non-glycosylated form. This post-translational modification is important for the structure and function of the hormone.

For Ela, our VP of R&D, glycosylation is one of the most interesting aspects of PRL-Fc – not necessarily for the protein itself, but for the implications of our fruit fly expression system, the EntoEngine.

Women in STEM - Future Fields VP of R&D Ela in Future Fields' lab

Ela in Future Fields' lab.

“Glycosylation is something that our EntoEngine does naturally,” Ela says. “PRL-Fc available on the market is produced by HEK293 cells, which are known for their ability to produce glycosylated proteins. We are the first one to show that Drosophila melanogaster is also capable of producing glycosylated, functional PRL-Fc."

Further analysis of the N-glycosylation pattern in our PRL-Fc is planned to reveal its impact on the stability and functionality of the protein. More information on glycosylation studies can be found in our recent prolactin performance report.

Scaling up protein production with fruit flies

Future Fields is the first to offer commercially scalable insect expression based on transgenic insects. PRL-Fc is a testament to our successful scale-up of producing a sensitive protein. Janelle, our Biomanufacturing Lead, has spearheaded scaling our manufacturing efforts for industry, including the mass production of our recombinant human prolactin.

Taking the prolactin protocols from the Protein Biochemistry team, Janelle swaps the production outputs from micrograms to milligrams per run. Everything is thoroughly documented to ensure that the protein is produced the same every time. From chemicals used to make the buffers, to the final product, every step is tracked for quality control and assurance.

Future Fields recombinant human prolactin
Women in STEM - Future Fields Biomanufacturing Lead Janelle holding a tray of recombinant human prolactin

Left: A close-up photo of Janelle holding Future Fields' prolactin. Right: Janelle holding a tray of Future Fields' prolactin after a manufacturing run.

“The most exciting thing about scaling up prolactin is that it can act as a model for difficult to produce proteins,” says Janelle. “Prolactin is a tricky protein, and being successful with this one, we can have more confidence and higher probability of success with even more challenging proteins in the future.”

From our lab to yours

We’re thrilled to offer an affordable, reliable supply of recombinant human prolactin for researchers around the world. With applications in both food and health research spaces, prolactin can support research in lactation insufficiency and milk composition in breastfeeding mothers; cultivated milk products and specialized infant formulations; immune and neuronal cell research; and beyond.

Want to learn more about how our prolactin protein can support your research and product development? Our performance report is available for free download here. Researchers can also request a free sample from our site to try it in their labs. Get your sample before it’s gone!


Future Fields' fly-derived Recombinant Human Prolactin at a glance:

  • Bioactive, > 90% purity
  • Cleaveable Fc-tag
  • N-glycosylated
  • Lyophilized
  • Negative for mycoplasma
  • Below threshold for endotoxin
  • Lowest price of prolactin on market

View product page and performance report below.

Don't want the Fc tag? Prolactin (Tag-Free) is now available!