Model host organisms for biomanufacturing are strains where the necessary experimental tools and fundamental data to direct metabolism via genetic manipulation have been developed, enabling rational metabolic engineering. However, interest in commercial deployment of nonmodel microbes is increasing 1, 2, 3•, 4. By domesticating organisms that are innately more suitable to industrial conditions, synthetic biology efforts can be more narrowly focused on optimizing substrate utilization, product titers/rates/yields, and cell growth/maintenance 5, 6, 7•, 8, 9, 10. Expanding the scope of domesticated hosts for biomanufacturing is also critical for expanding the repertoire of feedstocks and products accessible for bio-based manufacturing 3•, 11, 12, 13, 14. Experimental validation of the utility of novel hosts has been demonstrated through improved rates of production, unique biochemistries, production under nonstandard conditions, and utilization of unique feedstocks 4, 8, 15, 16, 17••, 18, 19. Furthermore, the design, creation, and cultivation of physiologically diverse strains that remain genetically stable and retain performance metrics over time in the presence of diverse feedstocks and products will reduce the costs involved in the development and scaling of biological production 5, 8, 15, 16, 18, 19, 20, 21••.

DNA delivery and gene editing approaches that can target a wide range of undomesticated microorganisms are rapidly being developed to reduce the time and resources that would otherwise be required for organism-specific procedures 5, 9, 14, 22, 23, 24, 25, 26•, 27, 28. These approaches have launched an unprecedented wave of efforts to engineer metabolic pathways in metabolically, physiologically, and phylogenetically diverse emerging hosts 4, 7•, 13, 17••, 18, 19, 22, 26•, 29, 30, 31, 32, 33. Notwithstanding these transformative advances, relatively few organisms have been developed, or ‘domesticated’, to the point that they could be considered established industrial platforms — where rational metabolic engineering could be applied rapidly toward a bioproduction goal 2, 5, 15.

Organisms often share traits that have led to their evolution into canonical bioproduction chassis strains, including rapid growth, ease of use in the laboratory (safe, genetic tractability, etc.), genetic stability, performance at scale, etc. 15, 21••. Another common thread among the progression of microorganisms into established hosts is that their development was undertaken by a multitude of groups, often using disparate approaches, for a myriad of purposes. Thus, accessing comprehensive and current information regarding the developmental status of different hosts for industrial applications is time consuming and requires access to many sources of information [15]. Although eventually successful with a handful of strains, a haphazard, slow approach cannot support the needs of a burgeoning biomanufacturing industry (Figure 1a).

Another critical gap in the pipeline for developing nontraditional hosts is access to a portal for tracking strain development. However, there are few resources designed to support host strain selection and development. The ChassiDex database (https://chassidex.github.io/) was built as a project for the International Genetically Engineered Machine Competition in 2017 and provides information such as available strains, growth media, BioBrick parts, metabolic models, key references, transformation and other protocols, vectors, and genome information for 23 hosts, including bacteria and fungi [34]. More recently, in 2023, the Cultivarium portal (https://www.cultivarium.org/) was developed and provides a wealth of information on 128 microbial strains with the goal of providing ‘open-source tools and assays designed for use in multiple microbes to minimize trial-and-error time in new species’. The portal emphasizes culture, molecular, and sequencing information and is particularly useful for early-stage development of nonmodel hosts. Finally, the MCF2Chem knowledge base, published in 2023, provides information on product formation data, culturing and fermentation conditions, and genetic methods [12]. It can be queried to recommend hosts suitable for synthesizing specific compounds. These types of portals will be critical for coordination of community-based chassis development efforts.

We propose that systematic, intentional, coordinated approaches can be applied to greatly improve the speed and efficiency of host selection and development (Figure 1b). Here, we introduce the Tier System for Host Development (Tier System), which has been created to aid in organizing, standardizing (to the extent possible), and communicating host development activities. We outline the objective and structure of the Tier System, list and briefly describe the underlying capabilities/data sets/knowledge that comprise the Tier System, and describe how the Tier System can benefit the wider bioproduction community.