Why outsource your microbial natural product discovery or bioengineering campaign?
Natural products offer immense potential across a wide range of industries from fungal biosurfactants, terpene fragrances and protein sweeteners in consumer goods and food ingredients, to complex API intermediates, antibiotics, insecticides and herbicides in pharma and agritech.
Yet unlocking that potential is rarely straightforward. The source organisms often come with real limitations: plants with supply or cost constraints, fungi or bacteria with no established scale-up processes. Sometimes the natural product itself is close to what's needed but not quite right and finding the right analogue can make all the difference.
Turning promising biology into a viable product demands deep expertise across multiple disciplines — molecular biology, microbiology, fermentation, protein biochemistry, biocatalysis, bioinformatics, analytical chemistry and process chemistry. Building that breadth of capability in-house is costly and complex.
That's where Isomerase comes in. Our multidisciplinary team of scientists and project leaders brings together all of these capabilities under one roof. With over a decade of experience delivering projects for partners across diverse sectors, we work closely with our clients to meet both immediate and long-term goals."
What are the keys to a successful microbial bio-based project?
A typical project centres on designing, building and optimising a microbial strain and the processes around it to produce a specific small molecule or metabolite.
The bar is high. A successful strain must meet demanding performance criteria:
- Verified product identity - confirming the molecule is what it needs to be
- Strong titre, rate and yield - ensuring commercially relevant productivity
- Minimal, manageable by-products - simplifying purification and reducing waste
- Stable genotype and phenotype - delivering consistency across generations
- Reliable scalability - performing predictably in fermentation at scale
- Efficient downstream processing - enabling practical, cost-effective recovery
- Acceptable cost of goods - making the route commercially competitive
- Defensible IP and freedom to operate - protecting the investment
Alongside strain development, we provide the robust data our partners need to evaluate whether microbial production can become a scalable, cost-effective manufacturing route with real commercial potential.
What is Isostream?
Isostream is our suite of technologies for chemical production in microbial systems, spanning bio-based commodity chemicals to natural product discovery and development, from strain sourcing and bioengineering to scalable upstream and downstream processing and CDMO tech transfer.
What are the keys to a successful natural product discovery and/or development project?
A successful natural product discovery / development project relies on a number of key factors. Initially, there needs to be a clear strategic focus and target selection (or target product profile). In many cases, the client has a clear business case for the product and understands the cost of goods required at scale to meet these objectives.
Accessing and producing a target natural product can be challenging due to limitations in native sources (such as plants), including low yields, scalability issues, and genetic intractability. The biosynthetic pathway itself may be complex, poorly understood, or incompatible with efficient production. Internal capability gaps and underperforming existing processes further hinder progress, with additional risks around IP, impurity and stability. To deal with these risks, a team with a broad range of interdisciplinary expertise is critical along with excellent communication and project management.
The team at Isomerase have successfully completed hundreds of projects with partners. We can support at every stage of the process, from concept to commercialisation. Unlike most partners, we also don’t charge downstream royalties for use of any of our technologies – we are also careful in managing costs throughout the process, making us a perfect choice for industries and sectors where cost of goods and project budgets need to be lower.
What are the typical stages of an outsourced Isostream microbial natural product / small molecule project?
1. Opportunity definition
Business development, with support from technical specialists will help establish clear alignment on the required target product(s), objectives, constraints, and commercial goals. They will work with you to define success criteria, decision points, IP considerations, and data requirements. Following this, the engagement will be formalized through an initial Statement of Work (SoW) and a dedicated project lead will be appointed as the main contact for the duration of the project, Business development will remain engaged to discuss and agree any additional work packages as needed.
2. Candidate discovery and sequence prioritisation
Utilising bioinformatics and microbiology expertise and tools, we can identify and source potential biosynthetic genes, pathways, and related components from diverse datasets and strain collections, including the substantial Isomerase strain collection, then prioritise candidates based on functionality, novelty, feasibility of expression, host compatibility, pathway coherence, and IP/FTO considerations.
3. Assay development
Utilising natural products chemistry and analytical chemistry expertise, we can convert target product profiles and business requirements into measurable specifications, develop assays to monitor product formation and process performance, and standardise scalable, transferable analytical methods for ongoing use.
4. Gene synthesis, expression and screening
Utilising molecular biology and bioinformatics expertise and tools, we can design and construct optimised genetic pathways and changes, introduce them into microbial hosts using appropriate engineering methods (which we are experts at developing de novo), including commercial use to Crispr and other rapid gene editing methods, and screen resulting strains to identify top performers based on productivity, growth, stability, and product quality.
5. Hit validation and manufacturability assessment
Utilising methods developed in section 3, we can verify product identity and accurately measure production using reliable analytical techniques. We can then use flasks or stirred tank reactors (STRs) to produce prototype material batches for partner evaluation and independent validation and generate variants or analogues if needed to assess performance against the target profile. We can evaluate key factors such as strain growth, pathway stability, genetic integrity, toxicity, by-product formation, precursor requirements, rate of production and early cost-of-goods. Use these insights to identify potential manufacturability risks before advancing to further strain optimisation or process scale-up.
6. Gene cluster, pathway and enzyme engineering / optimisation
Where needed, we can enhance pathway performance by optimising key enzymes, tailoring reactions, precursor supply, cofactor balance, expression levels, compartmentalisation, and product export. We can leverage rational design, bioinformatics, and machine learning approaches to maximise efficiency while minimising experimental complexity. We can apply iterative design–build–test–learn cycles to boost production and pinpoint the primary drivers of strain performance.
7. Strain improvement & production host optimisation
Once there is a microbial strain and process producing the product of interest, the journey can then move to improving performance. This can involve improving characteristics such as titre, pathway compatibility, genetic tractability, robustness, and scalability. The strain can be optimised by enhancing precursor supply, removing competing pathways, fine-tuning gene expression, balancing metabolic flux, improving cofactor availability, increasing product tolerance, and enabling efficient export. We can apply methods such as targeted genome editing, pathway refactoring, adaptive laboratory evolution (ALE), mutagenesis, and selection (such as classic strain improvement (CSI)) as appropriate. We look to validate consistent productivity, reproducibility, and genetic stability across multiple cultures and fermentation runs, and designate the lead strain for downstream process development and scale-up once the client productivity requirements are met.
8. Bioprocess development and scale-up readiness
Our skilled bioprocess team at our Solopark site usually takes over a project once it reaches this stage. We look to define target process and manufacturing goals, establish baseline small-scale performance, and optimise fermentation conditions to improve productivity and robustness. We assess scale-up risks through modelling and engineering analysis, implement controls and key parameters, and generate reliable bench-scale data (eg at 3-7L scale) to support successful scale-up.
9. Downstream process development (DSP) and optimisation
Our team of chemists and DSP engineers can help define product quality, regulatory, and cost targets, then develop and optimise scalable downstream processes for recovery and purification. We aim to balance purity, yield, robustness, and cost while maintaining product stability, and deliver a fit-for-purpose final product format.
10. Pilot scale production
Utilising our in-house 20-30L fermentation stirred tank reactors (STRs) or by managing the tech transfer process to one of our trusted CDMOs we can conduct pilot-scale fermentation and manage downstream processing to achieve the desired product format, and generate representative samples and data to support testing, regulatory planning, and manufacturing decisions.
11. Data package, tech transfer and next-phase plan
To support project regulatory and scale-up requirements we can provide comprehensive project deliverables including strain and construct information, assay protocols, analytical data, fermentation results, batch records, downstream processing details, risk assessments, and development recommendations. We can supply detailed process documentation covering flow schemes, titre/yield/productivity metrics, impurity profiles, analytical methods, operating ranges, and critical parameters to support pilot or commercial transfer. We also offer support for patenting and IP protection, including drafting embodiments and examples, conducting IP searches, and assisting with prosecution. We facilitate seamless transfer to the client, CDMO, manufacturing partner, or downstream development team.
How can outsourcing microbial strain engineering deliver greater efficiency, reduce risk, and maximise value for our customers?
Isostream scientific advantages:
- Instant access to world-class expertise across microbiology, synthetic biology, genome editing, pathway engineering, natural product chemistry, analytics, fermentation, and downstream processing—without the need to build it internally.
- Faster, smarter decision-making, with rapid identification of viable pathways, hosts, and engineering strategies—enabling confident early-stage go/no-go calls.
- Higher probability of commercial success, through the development of strains that deliver on titre, rate, yield, stability, and process compatibility.
Isostream commercial advantages:
- Avoid major capital investment, eliminating the need to build expensive in-house capabilities for engineering, screening, analytics, and fermentation.
- Engage on your terms, with flexible models spanning feasibility studies to full-scale strain and process development programmes.
- Control costs with confidence, through clearly defined work packages, milestones, and decision gates.
- Move faster to value-driving milestones, accelerating fundraising, customer validation, grants, partnerships, and strategic decisions.
