Bioprocess technology

Sophisticated robot screening and testing

Sophisticated robot screening and testing in highly instrumented laboratory bioreactors help to ensure our pipeline of new microbial strains for the production of enzymes at scales more than 200 million times larger than the volumes used in the laboratory tests.
Bioprocess-technology-2

Before we select a new microbial strain for scaling up to industrially relevant volumes, a number of laboratory tests are carried out to ensure that the strain will meet Novozymes’ performance requirements for improved, consistent yield and approved performance in the end application. At Novozymes this is achieved by using sophisticated tools for screening cell populations at single-cell level as well as developing cultivation processes that allow the cell to show its full potential for synthesis of the required enzyme.

Screening    

At Novozymes screening of single cells is accomplished by using equipment for aerobic cultivation at scales well below 10 mL or even below 1 mL. Combining these small volume cultivations with automated handling by means of robotics form the basis for a high throughput screening of single cells. Success with regard to picking the superior cell is only assured when using cultivation conditions suited for a particular expression system/host cell system. At Novozymes we use cultivation conditions developed by experts with in-depth knowledge of microbial physiology. The task of the microbial physiologists at Novozymes is to translate information about the genetic construct into conditions suited for cultivation and recovery at industrial scale.
 
 

Microbial Physiology   

Perhaps the most important tool of the microbial physiologist is a well-instrumented laboratory bioreactor, which allows in-depth studies of cellular growth, microbial metabolism, and enzyme expression while at the same time taking into account the existing production setup at the different Novozymes production sites worldwide. Novozymes R&D has a long-standing tradition of designing and building its own bioreactors for growing a number of different microorganisms.
Bioreactors equipped with sophisticated online sensors for monitoring the cellular metabolism allow the microbial physiologists to define the optimal cultivation conditions for enzyme yields. In some cases, highly specific sensors are developed at Novozymes as a result of close collaboration between molecular geneticists and the microbial physiologists. One example of such a sensor is a fluorescent probe for monitoring cell stress. Consequently, shortcomings in a potential production strain may be remedied at an early stage either by process adjustments or by changes to the genetic construct harbored by the cell.

Raw materials

Selecting the raw materials for a cultivation process is a multidisciplinary task combining knowledge on solubility, nutritional requirements, bioavailability, cellular metabolism, and pricing and worldwide availability of raw materials. At Novozymes we have more than 50 years’ experience in cultivating organisms – know-how that has enabled us to develop platform technologies for a number of microbial expression systems.