Fermelanta: Pioneering Bio-Manufacturing of High-Value Plant Metabolites

Fermelanta, a cutting-edge Japanese startup, is revolutionizing the bio-manufacturing landscape by engineering bacteria to produce valuable plant secondary metabolites, including morphine. Recently, the company secured a remarkable JPY 2 billion (approximately $13.6 million) in a Series A funding round.

The funding round was spearheaded by Universal Materials Incubator Co and Beyond Next Ventures, with additional backing from Angel Bridge, among others. The investment package also includes a grant from the Japanese government as part of the Deep Tech Startup Support Program, bringing Fermelanta’s total funding to JPY 4.8 billion (around $32.5 million).

Expanding Horizons: R&D and Scale-Up Capabilities

Fermelanta plans to utilize the newfound capital to broaden its R&D pipelines, enhance its ability to scale operations from laboratory to pilot stages, and bolster business development initiatives. The startup aims to collaborate with contract development and manufacturing organizations (CDMOs) to scale multiple product pipelines simultaneously.

“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,” stated Shogo Fukizaki, co-founder and CEO of Fermelanta.

Transformative Technology: The Power of Microbial Fermentation

Fermelanta is at the forefront of a significant advancement in synthetic biology, utilizing microbial fermentation to efficiently and sustainably produce plant-derived compounds. Historically, secondary metabolites such as benzylisoquinoline alkaloids (including morphine and codeine) have been costly to extract from plants, primarily due to the complexity of the metabolic pathways involved.

However, Fermelanta has successfully reproduced these enzymatic pathways using precision fermentation with microbes. “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,” explained Fukizaki.

Advantages Over Traditional Methods

While plant cell culture may appear to be a viable alternative for producing plant metabolites, Fermelanta leverages microbial fermentation technology, which offers several advantages:

• Ease and speed of producing target compounds using affordable media, ultimately reducing manufacturing costs and increasing production volume.
• Greater control over metabolic pathways as compared to plant cells, which can have complex feedback mechanisms making engineering challenging.

Despite the inherent complexities of constructing advanced metabolic pathways, Fermelanta believes that its microbial approach is reaching a pragmatic stage that surpasses traditional plant cell methods.

Business Model and Future Strategies

Founded in 2022, Fermelanta builds on 15 years of research conducted at Ishikawa Prefectural University, where the patents have been transitioned to the startup.

As part of a Phase 3 Fund Project with the Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Fermelanta is currently constructing a pilot plant featuring a 3,000-liter fermentation tank, anticipated to be operational by May 2026.

“Since the seed round in 2023, we’ve expanded our development pipelines and formed numerous business alliances. Our team has also grown in size, enhancing our capability to attract top talent,” added Fukizaki. “Our long-term goal is to develop the ultimate ‘synthetic organisms’ capable of producing various compounds at a low cost, thus creating a new sustainable industry.”

Product Pipeline Overview

Fermelanta’s diverse pipeline encompasses:

• Plant alkaloids for pharmaceutical and agricultural applications
• Flavonoids for nutraceuticals
• Carotenoids for flavors and fragrances
• Polysaccharides for cosmetics and food additives
• Vitamins and peptides

Currently focusing on pharmaceutical raw materials, particularly alkaloids, Fermelanta has expanded its product offerings from one to over ten, considering both in-house and collaborative projects.

Navigating Regulatory Landscapes

Fukizaki stresses that while drugs are typically subjected to rigorous and costly approval processes, the molecules Fermelanta is targeting for pharmaceutical applications are not novel. “We’re not engaging in drug discovery,” he noted. For compounds classified as active pharmaceutical ingredients (APIs) within generic drugs, simplified clinical trials should suffice, prompting the company to pursue collaborative partnerships.

In conclusion, Fermelanta is poised to transform the bio-manufacturing sector by leveraging innovative microbial fermentation techniques, ultimately setting the stage for a sustainable industrial future.