Fermelanta—a Japanese startup engineering bacteria to produce high-value plant secondary metabolites including morphine—has raised a JPY2 billion ($13.6 million) Series A round.
The round was led by Universal Materials Incubator Co and Beyond Next Ventures, with additional investment from Angel Bridge and others. It includes a grant from the Japanese government as part of the Deep Tech Startup Support Program and takes Fermelanta’s total funding to JPY 4.8 billion ($32.5 million).
The capital will be spent on expanding R&D pipelines, enhancing scale-up capabilities from lab to pilot stage, and business development, says the firm, which aims to work with contract development and manufacturing organizations (CDMOs) to scale up multiple product pipelines.
“We have established development capabilities for purification processes at laboratory and bench scales, enabling us to obtain tens of grams of product per batch, which can be used for research reagents and sample products. We are currently working with external CDMOs to establish a structure that can scale production up further, manufacturing from tens to hundreds of kilograms of product per batch,” cofounder and CEO Shogo Fukizaki told AgFunderNews.
“Fermelanta’s innovative bio-processes have the potential to transform industrial structures. Their platform technology based on multi-step gene introduction and precise control of cell systems is broadly applicable to a wide variety of plant-derived compounds.” Yusuke Shibafuji, Universal Materials Incubator Co
Multi-step metabolic pathways in microbial cells
Thanks to advances in synthetic biology, many food ingredients, nutraceuticals and pharmaceuticals are now produced more efficiently and sustainably via microbial fermentation.
Microbes are not, however, typically used to produce secondary plant metabolites such as benzylisoquinoline alkaloids (morphine, codeine, berberine, etc.), which are still extracted from plants in a costly and inefficient process because the metabolic pathways involved in producing them are so complex.
Fermelanta, however, has reproduced the enzymatic pathways to produce several of these molecules via precision fermentation with microbes, said Fukizaki.
“We have introduced an unprecedented number of up to 20 heterologous plant genes into the genome of a single bacterial cell that enable multi-step metabolic pathways.”
Plant cell culture might seem to be better placed than microbial fermentation to produce plant metabolites. However, Fermelanta’s tech—which enables complex multi-step metabolic pathways in microbial cells—comes with some key advantages, said Fukizaki.
“There are few examples where plant cell culture commercialized the production of rare ingredients for industrial applications, but it’s very hard to control and engineer complicated cells of high organisms like plants to improve productivity further because of negative feedback systems.
“The construction of complex metabolic pathways in microbial cells from scratch is still considered difficult and immature, but we believe our microbial approach is reaching a practical level that is better than plant cells in many cases.”
With microbial cells, “It’s easier to produce more target compounds and much faster to culture cells with cheaper media, which are critical for manufacturing cost reduction and mass production volume,” he added. “However, more complex compounds that require 40-50 steps/genes are still very hard to produce a mg/L titer via microbial fermentation.”
The business model and go to market strategy
Fermelanta, which was founded in 2022 but draws upon 15 years of research conducted at Ishikawa Prefectural University (the patents have been transferred to Fermelanta, says Fukizaki).
As part of a Phase 3 Fund Project with the Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), it has started construction of a pilot plant equipped with a 3,000-liter fermentation tank, which is scheduled to be completed in May 2026, said Fukizaki.
“Since the seed round [in 2023] we’ve increased our development pipelines and formed business alliances with multiple partners. We’ve successfully expanded our team, which is now one of our value points for attracting even more talented individuals to join us.
“Moving forward, we will begin the scale-up and validation process for samples and mass production, promoting the development of a new kind of bio-industry through future commercial production.”
Fermelanta’s long term goal is to “develop the ultimate ‘synthetic organisms’ that can produce whatever we want from low to high-molecular weight compounds, regardless of their structures, and at a low cost,” he added.
“We aim to create a new sustainable industry by bringing about a paradigm shift to the industrial structure that replaces traditional production methods relying on chemical synthesis and plant extraction processes.”
The pipeline
Fermelanta’s pipeline includes plant alkaloids for pharma and agriculture, plant flavonoids for nutraceuticals, carotenoids for flavors and fragrances, pigments and nutraceuticals, polysaccharides for cosmetics and food additives, vitamins, and peptides.
“We initially began with one pharmaceutical raw material and now have reached more than 10 including in-house and partnering projects,” said Fukizaki.
“For some compounds, we have achieved production yields at lab scale that can be less expensive than existing products if we produce those at a large scale. Currently, our most focused [advanced] product is an alkaloid for pharmaceutical raw materials and precursors, but other pipelines like flavonoids or carotenoids might go first depending on how the development proceeds.”
As for regulatory pathways, while drugs are more complex and expensive to get to market than foods and nutraceuticals, the molecules Fermelanta is looking at producing for pharma such as benzylisoquinoline alkaloids are not novel, stressed Fukizaki. “The chemicals themselves are the same as the ones already on the market. We’re not doing drug discovery.”
He added: “If the compounds are APIs [active pharmaceutical ingredients] in generic drugs, simplified clinical trials should be required. In that case, we plan to seek partners.”
The post Fermelanta nets $13.6m to engineer microbes for complex plant metabolite production appeared first on AgFunderNews.
