VALIDOGEN GmbH, a contract research and development organization focused on recombinant protein expression, strain engineering, and bioprocess development, has announced the release of a next-generation synthetic promoter library for methanol-free protein production in Pichia pastoris. Integrated into the company’s proprietary UNLOCK PICHIA® platform, the innovation expands options for high-efficiency yeast-based expression systems.
For more than 15 years, VALIDOGEN has supported clients using both methanol-induced and methanol-free production strategies. The newly developed synthetic promoter library marks a further evolution of its methanol-free approach, offering greater control over expression timing while delivering significantly increased product yields. Higher productivity directly contributes to lower cost of goods and enables more robust, scalable manufacturing processes.
Synthetic promoter architecture enables precision control
The promoter library is built on a synthetic design that combines engineered regulatory fragments with carefully selected sequence elements derived from native yeast promoters. This structure allows tunable and time-dependent activation of recombinant protein expression — without the need for external inducers such as methanol.
Throughout the entire process, glycerol or glucose serves as the sole carbon source. Eliminating carbon source switching reduces metabolic strain on the cells and supports sustained, high-level protein expression while minimizing stress-related productivity losses.
“VALIDOGEN has long been a pioneer in controlled methanol-free expression systems,” said Roland Weis, Head of Operations at VALIDOGEN. “We established this technology in industrial environments more than 15 years ago, with successful commercial implementation in bioreactors up to 200,000 liters. What distinguishes this new generation is the degree of precision and performance we can now achieve. Even with standard, non-optimized bioreactor protocols, we have recorded supernatant titers exceeding 20 g/L across multiple protein classes — matching and, in some cases, surpassing traditional methanol-induced systems.”
Expanding the UNLOCK PICHIA® portfolio with economic and operational advantages
Rather than replacing established methanol-induced AOX1-based systems — which remain available where appropriate — the new promoter library extends the flexibility of the UNLOCK PICHIA® platform.
According to CEO Thomas Purkarthofer, the benefits are both technical and economic. “This innovation enhances the range of solutions we provide to our customers. Increased productivity, simplified process management, reduced oxygen demand, and lower cooling requirements make methanol-free production highly attractive from both an operational and cost perspective. Additionally, manufacturers are no longer limited to facilities equipped to handle methanol at large scale.”
With this latest development, VALIDOGEN reinforces its position as a technology partner for scalable, high-performance recombinant protein production.
