Scaling-up production of plant endophytes in bioreactors: concepts, challenges and perspectives

Abstract

The benefit of microorganisms to humans, animals, insects and plants is increasingly recognized, with intensified microbial endophytes research indicative of this realization. In the agriculture industry, the benefits are tremendous to move towards sustainable crop production and minimize or circumvent the use of chemical fertilizers and pesticides. The research leading to the identification of potential plant endophytes is long and arduous and for many researchers the challenge is ultimately in scale-up production. While many of the larger agriculture and food industries have their own scale-up and manufacturing facilities, for many in academia and start-up companies the next steps towards production have been a stumbling block due to lack of information and understanding of the processes involved in scale-up fermentation. This review provides an overview of the fermentation process from shake flask cultures to scale-up and the manufacturing steps involved such as process development optimization (PDO), process hazard analysis (PHA), pre-, in- and post-production (PIP) challenges and finally the preparation of a technology transfer package (TTP) to transition the PDO to manufacturing. The focus is on submerged liquid fermentation (SLF) and plant endophytes production by providing original examples of fungal and bacterial endophytes, plant growth promoting Penicillium sp. and Streptomyces sp. bioinoculants, respectively. We also discuss the concepts, challenges and future perspectives of the scale-up microbial endophyte process technology based on the industrial and biosafety research platform for advancing a massive production of next-generation biologicals in bioreactors.

Metabolites Produced by Fungi against Fungal Phytopathogens: Review, Implementation and Perspectives

“…However, the little effort made so far by researchers and companies to develop the points from (vii) to (x) may explain the minimal relevance that this type of product currently has. One of the few works, in this case involving point (vii) (optimization of the fermentation conditions), is the aforementioned study carried out by Ganeshan et al [ 150 ], where a review of the concepts, challenges and perspectives regarding the scale-up production of plant endophytes in bioreactors is given. Therefore, these points should be strengthened in order to successfully implement these bio-products in agriculture.…”

“…A major investment is required for such an adaptation in a sector perhaps not mature enough yet, as the farmers’ unwillingness to use these products may indicate. Nevertheless, several studies, such as that of Ganeshan et al [ 150 ], have tried to help the industry translate the research from a laboratory scale to a large-scale commercial production manufacturing process by including the main steps for the optimization processes in bioreactors. However, more important than the production process may be the initial development of the active substance to be further produced and commercialized.…”

Early transcriptomic response of the mycoparasite Sphaerodes mycoparasitica to the mycotoxigenic Fusarium graminearum 3-ADON, the cause of Fusarium head blight

“…The rational classification of transcripts that encode proteins is critical for the effective utilization of genome sequences for functional and evolutionary studies (Tatusov et al 2000 ). This is of particular importance for microbial genome analyses (Galperin et al 2019 ) aimed at improving fungal and bacterial biotechnology as well as applications in agricultural settings to produce food commodities (Ganeshan et al 2021 ).…”

Bioengineered Enzymes and Precision Fermentation in the Food Industry

“…The technology has been in existence for a long time, but the knowledge base or expertise has been lacking. From a technical perspective, scale-up challenges include process development and optimization by judiciously selecting appropriate growth media, substrates, feedstocks, incubation temperature, and pH, and also considering the complexity of the fermentation process and downstream processing to obtain purified products [ 101 , 102 ]. Although precision fermentation allows for the specific molecule of interest to be produced efficiently, purification strategies can sometimes be still very complex.…”