Make
Bioforge: Our Manufacturing Platform.
Designing a molecule is one thing. Manufacturing it reliably, at industrial scale, is another. Most promising biologics don’t fail in the lab — they fail on the path to production. Yields drop. Costs escalate. Conventional chemistry hits structural limits. Programs stall.
BioForge is Constructive’s answer. It is a programmable cellular manufacturing platform built for novel protein and peptide manufacturing — including long-chain peptides and molecules carrying multiple non-canonical amino acids — at the scale and consistency that pharmaceutical and industrial partners need.
Where conventional peptide synthesis generates thousands of kilograms of toxic byproduct for every kilogram of product, BioForge enables biological production: cleaner, more scalable, and fundamentally better suited to the molecules the field is now trying to build.
How BioForge works.
BioForge integrates three capabilities that no other platform combines at this level.
The Syn61 chassis
BioForge is built on Syn61, the world’s first fully recoded organism. Its rewritten genome creates free codon slots that can be reassigned to non-canonical amino acids, and its altered genetic code makes it naturally resistant to the bacteriophages that disrupt conventional fermentation runs. Fewer batch failures. More reliable production.
Programmable translation
Engineered tRNA-synthetase pairs direct the Syn61 ribosome to incorporate new chemical building blocks at precise positions during protein synthesis. This happens biologically — inside a living cell — rather than through the step-by-step monomer additions and washes that chemical peptide synthesis requires. The result is that BioForge can produce complex, structurally demanding molecules that would be prohibitively expensive, unsustainable or technically impossible to synthesise chemically.
Industrial-scale fermentation
BioForge connects molecular precision to fermentation infrastructure. Engineered organisms produce target proteins through established microbial fermentation processes, enabling repeatable, scalable production. The same platform that works at bench scale translates to industrial output, without requiring a different manufacturing approach at each stage.
What BioForge makes possible.
The platform is designed around the molecules that conventional chemistry struggles with most.
These are precisely the molecules that next-generation biologics programs are trying to build. BioForge makes them manufacturable.
Long-chain peptides
Beyond the practical limits of solid-phase synthesis.
Multiple non-canonical amino acids
More than one new building block per molecule.
Scalable biomanufacturing of new-to-nature molecules
Using standard fermentation equipment, enabled by Syn61.
The manufacturing advantage, plainly stated.
Chemical peptide synthesis becomes exponentially harder as molecules grow longer or incorporate unusual amino acids. Yields decline. Waste multiplies. Production costs rise to the point where a molecule that works in the clinic becomes economically unviable at scale.
BioForge removes that constraint. Because production happens biologically — inside engineered cells, through fermentation — the platform scales without the yield degradation that plagues synthetic approaches. Partners can pursue more ambitious molecular designs because the manufacturing pathway exists to support them.
BioForge changes the question from “can we make this?”to “what should we make next?”
REFERENCES
Genetically programmed cell-based synthesis of non-natural macrocycles
Nature Chemistry 15, 61–69 (2023)
Demonstrates the encoded, cell-based synthesis of 25 diverse non-natural macrocyclic peptides — each incorporating two non-canonical amino acids — using Syn61Δ3-derived cells, showing the platform’s capacity to manufacture structurally complex molecules beyond the reach of conventional chemistry.
Adding disubstituted and beta-linked monomers to the genetic code
Nature 625, 603–610 (2024)
Breaks a longstanding barrier in genetic code expansion by developing tRNA display, enabling the site-specific incorporation of entirely new classes of monomers — including β-amino acids and α,α-disubstituted amino acids — into proteins within a living organism, substantially widening the chemical scope of what BioForge can manufacture.
Sense codon reassignment enables viral resistance and encoded polymer synthesis
Science 372, 1057–1062 (2021)
Shows how evolving Syn61 to delete the tRNAs decoding its freed codons creates complete resistance to a broad range of bacteriophages, while simultaneously enabling the incorporation of three distinct non-canonical amino acids — the foundation of BioForge’s reliability advantage in industrial fermentation.
Genetic code-locking confers stable virus resistance
Biochemistry 64, 3093–3103 (2025)
Demonstrates that encoding essential genes according to a refactored genetic code locks that code in place, converting temporary phage resistance into stable, long-term protection — a key advance for maintaining manufacturing reliability across extended production runs.
