Summary
A bioRxiv preprint reports valerolactam production in engineered Corynebacterium glutamicum, reaching 3.6 g/L after pathway design and fed-batch process optimization.
A bioRxiv preprint describes an engineered strain of Corynebacterium glutamicum that produced 3.6 g/L of valerolactam in a carbon-limited fed-batch process. The researchers combined genetic pathway design with control of glucose supply and dissolved oxygen to improve production while limiting unwanted by-products.
Valerolactam is a bio-based monomer, meaning it can serve as a building block for polyamide materials. The study focuses on making it through microbial fermentation rather than treating the result as a finished polymer product. The work was posted on September 18, 2026, and is presented as a preprint.
Engineering a route through 5-aminovalerate
The production challenge addressed by the study is the conversion of 5-aminovalerate, or 5AVA, into valerolactam. The authors identify inefficient cyclization of 5AVA, formation of competing products and insufficient process control as barriers to microbial production.
To build the route, the researchers engineered C. glutamicum to express davBA from Pseudomonas putida and lysP from Escherichia coli. They then introduced avaC from Collinsella intestinalis, which enabled conversion of 5AVA to valerolactam. This combination allowed the bacterium to form valerolactam while accumulating only small amounts of L-lysine, 5AVA and glutarate in flask cultivations.
The use of genes from different microorganisms is an example of metabolic engineering: a host cell is given or modified with biochemical functions so that carbon is directed toward a desired compound. In this case, the engineered pathway was paired with fermentation conditions designed to keep more of that carbon in the target product.
Oxygen and glucose changed the fermentation outcome
Batch bioreactor experiments showed that process conditions strongly affected the result. Increasing the glucose concentration raised valerolactam titres, but it also increased the accumulation of by-products. Raising the dissolved-oxygen setpoint from 30% to 50% improved cell growth and volumetric productivity.
The researchers also measured intracellular cofactors, molecules that help cells transfer energy and electrons during metabolism. Those measurements showed a decline in energy status and changes in redox balance as production progressed. The findings indicated that pathway design alone was not sufficient; carbon availability and oxygen supply also shaped how effectively the cells produced valerolactam.
The best reported result came from carbon-limited fed-batch cultivation at 50% relative dissolved oxygen. In this process, nutrients are supplied during fermentation while carbon input is controlled rather than provided all at once. The culture reached 3.6 g/L valerolactam, with a reported yield of 0.231 g/g and volumetric productivity of 0.075 g/L/h. The authors also report that this approach minimised by-product formation compared with conditions that supplied higher glucose concentrations.
The study therefore presents a combined pathway-and-process strategy: AvaC enabled the final conversion to valerolactam, while controlled feeding and oxygen management improved the fermentation result. The reported endpoints concern laboratory flask and bioreactor production of the monomer. The source does not report conversion of the product into polyamide or performance of the resulting material, and scale-up beyond the described cultivation work remains a further process-development question.