We have built a platform to discover and manufacture valuable natural products from fungi and other microbes. Our technology makes this process 10-100 times faster than traditional methods, which means we can bring new products to market more quickly and at a lower cost.

Please contact us at info@terrabioforge.com for technical information or to request a quote for Terra Bioforge’s research and lab services.

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MycoDrive™

A Breakthrough Platform to Accelerate High-Yield Fungal Production

MycoDrive™ is a next-generation genome engineering platform that turns filamentous fungi into ultra-efficient production hosts—delivering dramatically higher yields in a fraction of the time.

For markets where production output determines whether a product can scale or succeed, MycoDrive unlocks the high titers needed to accelerate development, reduce costs, and bring valuable fungal innovations to market faster.

Applications & Benefits:

• Boost product yields for natural products, BGCs*, and enzymes — enabling products that were previously too low-producing to be viable
• Lower manufacturing costs (COGS) by creating smarter, more efficient production strains
• Engineer in the best host for the job — whether improving the native organism or moving production into a faster, easier-to-scale microbe
• Accelerate development timelines with more high-performing strains available for rapid testing and scale-up

 

• *A Biosynthetic Gene Cluster (BGC) is a compact set of genes inside microbes that functions like a ready-made manufacturing line. Each cluster produces a specific high-value product — such as a therapeutic, bioactive compound, enzyme, food ingredient, or material — and can be switched on, optimized, or repurposed for commercial use.

  • Why this matters: MycoDrive technology allows companies to rapidly turn microbes into scalable production systems, shortening development timelines and enabling new product pipelines in health, food, and sustainability markets.

• *AMA1 is a DNA element that allows fungi to rapidly and flexibly express multiple copies of new genes — enabling faster strain development, higher product yields, and lower commercialization risk.

  • Why this matters: AMA1 accelerates development timelines, increases production yields, and reduces the cost and risk of bringing new fungal-based products to market—directly improving return on R&D and commercialization success rates. MycoDrive technology leapfrogs AMA1 plasmids by providing long-term genome integration stability and higher copy numbers of BGCs.
    

 

 

CASE STUDY – Heterologous Overproduction of Bikaverin

Bikaverin is a multi-gene purple pigment used to visualize expression strength. It’s pathway from Fusarium oxysporum was heterologously expressed in Aspergillus nidulans using MycoDrive technology to attain expression titers ~30x higher over incumbent genome engineering methods.

Ongoing work is expanding this transformative tool into new fungal hosts and further boosting native or heterologous production titers which will enable a shift in expectations for what synthetic biology can do for industrial mycology.

 

           

MycoDrive technology quickly attains highest titer

• Supplements BGC Refactoring
  • BGC refactoring is often necessary to convert a poorly expressed gene cluster into a high-performance manufacturing module suitable for scalable bioproduction.
• Straightforward cloning – no HOM arms or dealing with AMA1 repeats
  • HOM arms or Homology arms are used for homologous recombination during CRISPR editing — they show the cell exactly where to place new DNA, enabling accurate and efficient genome engineering.
• Heterologous titer in A. nidulans can beat native producer F. oxysporum

 

BGC Copy Number Positively Correlates with Heterologous Bikaverin

Over half of transformants generated with MycoDrive were high bikaverin producers. To better understand the relationship between BGC copy number and heterologous natural product production, digital PCR (dPCR) was used to quantify BGC copy number/genome. Integration frequency correlates with increasing bikaverin production up to ~5-10 copies/genome. More than that and, not surprisingly, there appears to be another production bottleneck which could be overcome with targeted genetic manipulations, process engineering, or even mutagenesis.

Random integration methods can oftentimes require screening 1,000s of transformants to find stable strains with intact payloads and high performance. MycoDrive engineering produces high performing clones early in the R&D process.

 

What can MycoDrive engineering do for you?

 

       

 

Let’s discuss how MycoDrive technology can advance your fungal product R&D and production!
Benjamin Knox, PhD – Director of Fungal Technology  bknox@terrabioforge.com                  https://vn7qtk8lp41.c.updraftclone.com/

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BIGDNA®

Tools for Manipulating BGCs

Natural products are made from recipes encoded with BGCs; historically, it has been very difficult to work with these large pieces of DNA. 

Our BIGDNA® tools, including DNAtrap®, allow us to capture and modify these entire recipes from any microbe, which is a critical step in developing new products.

• We can clone very large gene clusters (up to 150 kb) that are usually ‘impossible’ to move because they’re repetitive or GC-rich
• Effectively captures BGCs from complex genomic DNA (gDNA) or metagenomic library (DNA from uncultured environmental microbes, where many of the best natural products hide) substrates
• De-Risked: DNAtrap® has been used to clone >130 intact BGCs to date

 

Foundational Technologies for Complex Molecule Manufacturing

BAC (Bacterial Artificial Chromosome)
A large-capacity, stable DNA carrier that enables companies to move and express massive, high-value genetic programs—such as entire natural product pathways—inside production strains.

PKS (Polyketide Synthase)
A modular biosynthesis engine used by microbes to create valuable small-molecule products, including many blockbuster drugs, with tunable architectures that support rapid innovation.

NRPS (Nonribosomal Peptide Synthetase)
A natural molecular foundry that assembles complex therapeutic and industrial peptides with precision—unlocking access to differentiated products that can’t be made by standard biology.

Hybrid PKS–NRPS Systems
Integrated biosynthetic platforms that combine the strengths of both PKS and NRPS machinery, enabling discovery and scalable manufacturing of uniquely complex, high-margin molecules.

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Engineering Expression of BGCs

In both native and heterologous microbial hosts natural product production is an innately regulated process. These pathways are often naturally ‘switched off’ or very low, which makes their products hard to detect, measure, or optimize.

Our team has pioneered novel methodologies to predictably activate BGCs for both natural product screening and titer optimization workflows.

• BGCexpress® allows you to “switch on” natural product pathways only when needed, boosting yields while maintaining healthy growth.
  • The result: 2–3× higher titers that make it easier to identify promising molecules and advance the best candidates quickly.
• BGCrefactor® streamlines the redesign of entire biosynthetic gene clusters—quickly removing genetic roadblocks and enabling higher-performing production strains.
  • The result: A multiplexed, marker-free workflow simplifies pathway optimization end-to-end, accelerating the creation of improved natural product titers and more scalable biomanufacturing.

Together, these tools unlock previously silent or low-yield pathways and convert them into highly productive, tunable manufacturing systems—significantly accelerating optimization and time-to-value.

 

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Metabologenomics for Natural Product BGC Identification

Metabologenomics is a data-driven method that links what an organism can produce (from its genome) with what it actually produces (its metabolites). By combining genomic sequencing and metabolite profiling, it rapidly reveals which metabolic pathways are active and which ones could be turned into new, valuable products — like breakthrough drugs, enzymes, or specialty chemicals.

In short, Metabologenomics turns biological “blueprints” into commercial discovery opportunities faster and more efficiently.

One of the biggest barriers in natural product discovery is knowing which genes create which valuable molecules. Our patented Metabologenomics platform removes that guesswork. By combining advanced bioinformatics with AI-driven metabolite analysis, we can map every molecule a microbe makes back to its exact genetic “recipe”. This gives us a fast, reliable way to uncover previously hidden natural products — and then engineer them into scalable, commercially viable assets.

• Prospect Fungi is a proprietary analysis tool for in silico prediction and annotation of fungal BGCs
  • An AI platform that grows and learns from known BGC: Natural Product relationships
• Haystack-MS: Finding new drugs via targeted cloning
  • Solves needle-in-the-haystack problem of finding target compounds in complex metabolite mixtures
  • Rapidly identifies and produces natural products by heterologous expression

We’ve essentially automated the critical step of linking biosynthetic gene clusters to commercially valuable molecules, transforming trial-and-error discovery into a predictable, accelerated pipeline that reduces development risk.

 

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Hosts for Heterologous Expression

When it comes to optimal heterologous expression of natural products, host selection matters. Precursor metabolites, cofactors, among other host-specific variables can greatly influence the successful production of specific molecules. Our access to a suite of optimal heterologous hosts provides the greatest opportunity for natural product expression.

• CleanChassis™ strains utilizing the main industrial workhorses used in pharma, agriculture, and enzymes, have been engineered to reduce competing metabolite production:
  • Streptomyces, Bacillus, Aspergillus, and Gram Negative bacteria
• For every BGC of interest, our growing portfolio of CleanChassis™ strains represents an opportunity to accelerate optimal expression

 

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For additional information on Terra Bioforge technical capabilities, check out our conference posters on  New Tools for Targeted Cloning and Over Expression of Biosynthetic Gene Clusters and Expanding Functional Access to Fungal Natural Products with Metabologenomics and Heterologous Expression.