Each fermentation process is based on:
- specific endogenous metabolic pathway;
- introduction of exogenous genetic material, to provide a completely new capability.
PASSIVE SELECTION. The classical improvement is based on the screening of many cell lines (clones), testing the specific molecule production capability. The process is direct to identify clones able to produce a high concentration of specific secondary metabolites.
ACTIVE SELECTION. In order to speed up the strain improvement, to increase the variability, the strain can be modified by means of chemical (nitrose guanidine) and physical (UV) treatments. Otherwise, the selection can be based on the introduction of a specific molecule in the substrate.
GENE CLONING. The introduction of exogenous genetic material creates totally new strains with new potential.
Any specific microrganism strain needs specific parameters of growth to express the maximum potential, in particular for the following parameters:
- medium parameters and composition, including:
- sterilization procedure and temperature
- carbon source type and concentration
- nitrogen source type and concentration
- vitamin type and concentration
- oligoelements type and concentration.
- feeding strategy.
Fermentation technology (fermentation biotechnology)
It is a process based on the metabolism of microrganism, mainly bacteria and fungi.In specific condition of temperature, pH, substrate and oxygen, is possible to drive the microrganism metabolism in order to produce specific secondary metabolites based on endogenous metabolic pathways or new capability introduces by means of exogenous genetic material.
The scale-up allows implementation on an industrial scale a technology already defined on a lab scale. Several aspects has to be considered, including:
- pressure: in industrial scale a substantial gradient makes difficult to obtain a broth homogeneity.
- Surface/volume ratio: it influences several parameters, like foam, temperature regulation and homogeneity.
- Stirring: with high volume is not possible to reach too high impeller rpm (rotation per minute).
- Number of generation: a strain is stable when the specific cell production capability does not substantially decrease after the cell duplication. A scale up should identify the number of generations without production capability decreasing.
Industrial fermentation A completely defined fermentation technology is a process which faces all issues involved in the industrial production, including the:
- workability of the Harvest Broth: an unsuitable reology does not allow a reliable following broth treatment phase.
- Energy consumption.
- Applicability in industrial scale for feeding procedure and medium preparation.
- Cost: the process must be profitable when compared with chemical and extraction processes.
Down Stream Phase
It is the composite procedure to obtain the final Active Ingredient from the Harvest Broth, with the desired final quality. Usually, two main phases can be identified:
- recovery, which allows to separate the Active Ingredient from cell or cell debris phase, and makes a first step of purification; the bulk obtained can be called “crude”.
- Purification of the “crude”, which increases the purity of the final product.
The engineering of a plant must be at the same time:
- multipurpose, to follow the possible market variation;
- suitable for the specific process.
It can be:
- Process Engineering
- Preliminary Basic Engineering
- Basic Engineering
- Detailed Engineering
It is the target molecule of technology and production. It can be utilized in:
- Pharmaceutical (API: Active Pharmaceutical Ingredients)
- Food and Feed