Directed evolution services
Directed evolution CRO services for protein optimization — iterative mutagenesis library construction, yeast and mammalian display screening, and NGS-resolved variant selection for binding, stability, and catalytic activity
Start a project →What directed evolution is
Directed evolution applies the principles of natural selection in the laboratory. You start with a protein that partially meets your requirements — it binds the target, but weakly; it catalyzes the reaction, but slowly; it expresses, but poorly. Then you introduce diversity, apply selection pressure, and recover improved variants.
The process is iterative. Each round of mutagenesis and selection generates a population enriched for variants with improved performance. Over multiple rounds, the protein accumulates mutations that collectively shift its properties toward your specification.
At Ranomics, we screen high-diversity mutagenesis libraries (10^7-10^8 variants) using display platforms, functional enzyme assays, or custom reporter systems — all coupled to next-generation sequencing. Every variant in the library is tracked quantitatively across selection rounds, giving you enrichment data at single-sequence resolution rather than qualitative colony-picking results.
Random and focused mutagenesis, matched to your protein
Random mutagenesis
Error-prone PCR introduces random point mutations across the entire gene. The mutation rate is tuned to introduce 1-5 amino acid substitutions per variant, balancing diversity against the probability of catastrophic mutations. This is the standard starting point when you have no structural data to guide library design.
Focused mutagenesis
Site-saturation mutagenesis, combinatorial scanning, and degenerate codon libraries concentrate diversity at positions identified by structure, DMS data, or prior evolution rounds. This approach explores the sequence space where improvements are most likely to reside.
High-throughput screening by display and functional assay
The mutagenesis library is screened using the selection system matched to your functional requirement. Display-based selection for binding; reporter-based selection for activity; growth-based selection for fitness.
Yeast surface display
FACS/MACS selection against labelled target. Quantitative enrichment by NGS. 10^7-10^8 library capacity per sort.
Mammalian display
CHO or HEK293 display for proteins requiring native glycosylation or folding machinery. Lower throughput, higher fidelity.
Functional selection
Growth-based or reporter-based assays for enzyme activity, stability, or cellular function. Custom assay development available.
Multiple rounds of selection compound improvements
Each selection round enriches the population for variants with improved properties. Between rounds, the enriched population can be re-diversified (by error-prone PCR, DNA shuffling, or focused mutagenesis at newly identified positions) to explore the fitness landscape around confirmed improvements.
NGS readout after each round quantifies the enrichment of every sequence in the library. This data guides the design of subsequent rounds — identifying which positions are under selection, which mutations co-occur, and where additional diversity is likely to yield further improvement.
Random mutagenesis + broad selection. Identify regions under positive selection.
Focused mutagenesis at enriched positions. Increase selection stringency.
Combinatorial recombination of beneficial mutations. Fine-tune selection gates.
Targeted diversification at remaining positions. Maximize lead performance.
Directed evolution questions
What is the difference between directed evolution and rational protein design? +
Directed evolution does not require structural knowledge of the protein. It uses random or semi-random mutagenesis paired with high-throughput selection to find improved variants. Rational design (including AI-driven approaches) uses structural information to guide specific mutations. We offer both and often combine them in a single campaign.
What properties can you optimize through directed evolution? +
Binding affinity, thermal stability, expression level, solubility, catalytic activity, substrate specificity, and resistance to aggregation. We screen for whatever phenotype your assay can measure.
How many rounds of evolution are typically needed? +
Most campaigns run 2-4 rounds of mutagenesis and selection. Each round takes 3-5 weeks depending on library size and selection complexity. Improvements are measurable after the first round in most cases.
Do I need to provide a starting protein? +
Yes. Directed evolution requires a functional starting sequence. If you do not have one, our AI binder design service can generate de novo candidates as a starting point for subsequent evolution.
Ready to evolve your protein?
Tell us about your starting protein and optimization goals. We will scope a directed evolution program and get back to you within 24 hours.
Start a project →