## 1 Introduction  
Roots of land plants exude small molecules, oligosaccharides, and proteins into the soil. The secreted compounds called root exudates serve multiple functions: they facilitate mobilization of soil nutrients [1; 2; 3], modulate the composition of microbial communities of the rhizosphere [4], and attract or repel soil micro- and mesothelioma, affecting crop health and productivity [5]. Exudation of metabolites by roots is modulated by nutrient availability [6] and herbivore infestation [7]. Root exudates in turn serve as chemical signals for symbiotic and pathogenic microorganisms [8; 9; 10], soil herbivores and their predators [11]. Hairy roots are plant roots genetically transformed with the help of _Agrobacteriumum rhizegenes_ that exhibit neoplastic growth and can be maintained indefinitely in sterile media without externally added phytohormones [12; 13]. Because hairy root cultures consist entirely of differentiated roots and can be easily cloned, they are an ideal model for studies of root biochemistry [14; 15] and root-specific processes such as nodulation [16] and the synthesis of root-specific metabolites [17]. Hairy roots also proved useful in studies of interactions between crop plants and herbivores [18]. Biomass production in hairy root cultures is higher than in callus or suspension cultures, therefore hairy roots have been exploited for the production of plant secondary metabolites [12; 19; 20; 21]. This strategy appearsparticularly promising for large-scale production of metabolites that are primarily synthesized in the roots, such as certain tropane alkaloids of medical interest [23] and glucosinolates with chemoprotective potential [24]. Optimization of the activity of desired biosynthetic pathways can further increase the efficiency of secondary metabolite production by hairy roots [25; 26; 27; 28]. Recently genetic engineering of hairy roots received a boost by an adaptation of CRISPR/Cas9 technology for delivery by _A. rhizogenes_, which combines genome editing and hairy root induction into a single step [29]. Root exudates of hydroponically grown genetically engineered plants [30] as well as hairy roots of genetically modified plants [31; 32] can also be used for the production of proteins for diagnostic and medical purposes such as antibodies, antigens for immunization, and growth factors. Optimization of the production system requires comparing multiple genetically enhanced lines because the efficiency of promoters used to drive heterologous gene expression varies among transformation events and even among different parts of the same plant [33]. Similarly, the expression of target genes and the yield of the desired products varies among hairy root lines [21; 28]. Production of natural products by plants that have not been genetically engineered requires testing multiple accessions, too, because secondary metabolite synthesis varies among plant accessions in a way that is often not predictable based on the genotype [34; 35]. Furthermore, cultivation conditions strongly affect production of plant secondary metabolites in hydroponics [36] as well as in hairy root cultures [21; 37]. For these reasons, multiple cultures have to be grown in parallel during the optimization of hairy root-based production systems. A major challenge for hairy root cultures is the supply of oxygen [38]. Different concepts have been pursued to improve oxygen supply to hairy roots in mid- and large-scale bioreactors [22; 39]. Apart from conventional stirred bioreactors [40] and stirred bioreactors modified to reduce sharing damage [22; 41], hairy root cultures have been grown in plastic sleeve reactors [42], bubble reactors [43], mist reactors [44; 45], airlift reactors [46], and liquid-dispersed reactors [47]. The implementation of these concepts focused on midscale bioreactors for research on hairy roots and on industrial bioreactors.