Streptomyces Fermentation Services

With over 20 years of microbial fermentation experience and a comprehensive strain development platform, BOC Sciences provides a full range of fermentation services based on various organisms. Streptomyces is the largest genus of Actinobacteria that has been widely recognized for its potential for producing bioactive secondary metabolites such as antibiotics, which is also one of the key microorganisms involved in building our strain development platform. BOC Sciences' strain development platform can help our global customers to obtain desired active products, including novel antibiotics and heterologous expression of proteins. Nevertheless, BOC Sciences offers microbial fermentation services from laboratory concepts to commercial-scale manufacturing that uses Streptomyces as host cells to develop and produce valuable products.

Introduction of Streptomyces

Streptomyces is a Gram-positive bacteria, commonly found in soil and insect microbiomes, and is the largest genus of Actinobacteria from the family Streptomycetaceae. In fact, Streptomyces are part of multiple ecosystems and are known to produce chemically diverse metabolites, including most clinically relevant antibiotics.

Streptomyces are filamentous, spore-forming bacteria whose life cycle is complex and includes stages of aerial hyphae formation on the soil surface to produce spores; Subsequently, the spore germinates in plant roots and produce filamentous colonies. Streptomyces are capable of forming complex substrate mycelium that contributes to the removal of organic compounds from substrates.

Typically, Streptomyces uses large enzymatic complexes to synthesize antibiotics, such as polyketide synthase (PKS), non-ribosomal peptide synthase (NRPS), or a combination of both. These large multi-enzyme complexes use different domains to accomplish chemical modifications and afford a wide range of antibiotics

Advantages of Streptomyces Fermentation

Strain culture of Streptomyces

The cell wall of Streptomyces is composed of peptidoglycan, which helps maintain osmotic pressure and facilitates its survival in different environments. Streptomyces can survive in various environments mainly due to the presence of pigments and aromas within its spores that stimulate cell development and secondary metabolites production.

Metabolite production of Streptomyces

Streptomyces are abundant and versatile soil microorganisms due to high metabolite production, rapid biotransformation processes, ability to degrade lignocellulose and chitin, and their roles in organic substances' biological cycle.

Protein expression of Streptomyces

Streptomyces can be used to express eukaryotic proteins. In general, E.coli is often used to express eukaryotic genes due to its ease of gene manipulation. However, using the E.coli system, protein misfolding can often lead to insolubility, deposition of inclusion bodies and loss of biological activity. In contrast, secretion by Gram-positive bacteria, such as Streptomyces, can direct secretion into the extracellular medium, facilitate the industrial production of heterologously expressed proteins as it simplifies the subsequent purification steps, and ultimately increase overall yield.

Applications of Streptomyces Fermentation

• Soil-dwelling Streptomycetes, such as Streptomyces coelicolor, colonize plant roots to provide plant protection from potential phytopathogens through antibiotic secretion. Industrially, the production of antibiotics by Streptomyces through fermentation offers a potentially sustainable solution for improving crop yields. Furthermore, Streptomyces produces various antifungal compounds of high medicinal value, including nystatin, amphotericin B and natamycin.
• Streptomyces coelicolor is a model organism for studying Streptomyces, a Gram-positive bacteria that undergoes a complex life cycle and produces bioactive metabolites and extracellular enzymes. The study of bacterial differentiation and production of bioactive molecules in S. coelicolor contributes to discovery and fermentation of essential compounds in the medicinal field.
• Approximately half of the clinically used antibiotics and other critical pharmaceutical products of nature were produced originally by Streptomyces. Streptomyces is capable of producing a variety of bioactive secondary metabolites, such as antifungals, antivirals, antitumors, anti-hypertensives, immunosuppressants, and especially antibiotics. The fermentation development of Streptomyces allows the industrial expansion of these valuable compounds.

Project Workflow of Streptomyces Fermentation

• Customer advisory
• Project discussion
• Streptomyces served as host cell
• Strain improvement and fermentation development
• Novel strain evaluation
• Project delivery

References

1. Gerry A. Quinn, Streptomyces from traditional medicine: sources of new innovations in antibiotic discovery, J Med Microbiol, 2020, 69(8): 1040-1048.
2. Yunci Qi, et al. A comparative metabologenomic approach reveals mechanistic insights into Streptomyces antibiotic crypticity, PNAS, 2021, 118, e2103515118.
3. Rudi Emersonde Lima Procópio, Antibiotics produced by Streptomyces, Braz J Infect Dis, 2012, 16(5):466-471.