A Breakthrough for High-Throughput Screening

October 15, 2021

A common challenge of fermentation-based manufacturing is selecting the right manufacturing strain that will best support the production of the target molecule. In order to identify the best possible strain, synthetic biology teams rely on high-throughput screening (HTS) to rapidly screen hundreds of thousands of strains and narrow down the best candidate. With nearly 20 years of experience bringing bio-based products to market, Amyris has honed a unique approach to HTS that is rooted in running scaled-down fermentations that mimic the process at pilot scale, and eventually, industrial scale.

The Amyris HTS team – consisting of operations engineers, analytical chemists, biochemists, and automation engineers – considers several factors in the screening phase, including how effective and fast the strain is at turning feedstock into product, the strain’s health, and its ability to grow during fermentation. Choosing the right strain early in the process reduces time and cost in the fermentation phase and ultimately, brings bio-based products to market faster. Compared to 2012, Amyris has decreased average time to market by 80 percent and lowered average product development cost by 90 percent. The HTS phase is a critical component of the proven Amyris Lab-to-Market™ operating system that drives Amyris’ success in delivering on synthetic biology’s potential.

Amyris’ mission is to accelerate the world’s transition to sustainable ingredients. To realize that mission, the company has remained committed to continued innovation. This is demonstrated by a recent collaboration with Berkeley Lights, a platform for digital cell biology, to explore new approaches to HTS for achieving greater speed and scale. In a new paper, published in partnership with Berkeley Lights, Amyris has shown early success using microfluidics for HTS for one of its target molecules. Already the new workflow has halved the time required for screening new yeast strains and eliminated around 90 percent of the plastic, chemicals, and labor required in the previous process. Additional benefits include:

  • Less liquid transfer, which can help reduce the margin for error.
  • Significantly sizes down the physical space requirements – in this new process, the combined volume for thousands of miniature cultures is about the size of a quarter, which frees up space in the lab for other equipment and dramatically decreases how long it takes for the cells to grow, which can save weeks of experimentation.
  • More closely mimics a bioreactor by tightly controlling nutrient levels, oxygenation, and pH balance during growth to better predict how strains will behave before testing them in the fermentation phase.

Through this work, Amyris has demonstrated that predicting the behavior of a target molecule in fermenters (roughly a billion times larger in volume) can be made more efficient and successful. This is an exceptional example of pairing cutting-edge technologies to further advance the synthetic biology industry and bring new innovations to market.

This type of exploration allows Amyris to continue delivering on the promise of synthetic biology and bringing products to market that are effective, sustainable, and accessible. This paper marks an exciting first step and the Amyris HTS team aims to build on this foundation to expand its use with other molecules in the pipeline.

To learn more about Amyris’ work with Berkeley Lights, read the full paper, published by leaders from the Amyris and Berkeley Lights R&D teams: High-throughput optofluidic screening for improved microbial cell factories via real-time micron-scale productivity monitoring.

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