Morphogenesis of Streptomyces in Submerged Cultures

Abstract

Members of the genus Streptomyces are mycelial bacteria that undergo a complex multicellular life cycle and propagate via sporulation. Streptomycetes are important industrial microorganisms, as they produce a plethora of medically relevant natural products, including the majority of clinically important antibiotics, as well as a wide range of enzymes with industrial application. While development of Streptomyces in surface-grown cultures is well studied, relatively little is known of the parameters that determine morphogenesis in submerged cultures. Here, growth is characterized by the formation of mycelial networks and pellets. From the perspective of industrial fermentations, such mycelial growth is unattractive, as it is associated with slow growth, heterogeneous cultures, and high viscosity. Here, we review the current insights into the genetic and environmental factors that determine mycelial growth and morphology in liquid-grown cultures. The genetic factors include cell-matrix proteins and extracellular polymers, morphoproteins with specific roles in liquid-culture morphogenesis, with the SsgA-like proteins as well-studied examples, and programmed cell death. Environmental factors refer in particular to those dictated by process engineering, such as growth media and reactor set-up. These insights are then integrated to provide perspectives as to how this knowledge can be applied to improve streptomycetes for industrial applications.

Taxonomy, Physiology, and Natural Products of Actinobacteria

“…Interestingly, production of enzymes through the twin arginine translocation (Tat) exporter occurs closely behind the hyphal tips in S. coelicolor (16,394); in line with this concept, Tat substrates are secreted more efficiently in fragmenting strains of S. coelicolor and S. lividans (313). An extensive review of the industrial implications of the correlation between growth and natural product formation is be-yond the scope of this review, so we refer the interested reader elsewhere (24,(395)(396)(397)(398).…”

“…A complex relationship exists between morphology and antibiotic production. Streptomycetes display a great many different morphologies in submerged cultures, ranging from fragmented growth to dense clumps, and this can have a major influence on their production levels (24). For example, in Saccharopolyspora erythraea, erythromycin production is favored by clumps with a minimum size of around 90 m in diameter (383).…”

“…Except for Sporichthya sp., which produces aerial hyphae that are initiated upright on the surface of the medium by holdfasts, Actinobacteria form a substrate mycelium in both submerged and solid-grown cultures. However, on solid surfaces, many differentiate to form aerial hyphae, whose main purpose is to produce reproductive spores (23,24). The substrate mycelium develops from outgrowth of a germinating spore.…”

Aggregation of germlings is a major contributing factor towards mycelial heterogeneity of Streptomyces

“…This mode-of-growth leads to the construction of complex networks of interconnected hyphae called mycelia. When grown in liquid, these mycelia display markedly different morphologies5. Some strains, including the industrial workhorse Streptomyces lividans , predominantly form dense mycelial particles called pellets.…”

Heterogeneity in the Histidine-brace Copper Coordination Sphere in Auxiliary Activity Family 10 (AA10) Lytic Polysaccharide Monooxygenases

“…In liquid-grown cultures, the growth of many streptomycetes is characterized by the formation of large biofilm-like aggregates, called pellets (24,25). The competence of streptomycetes to directly secrete enzymes into the culture broth makes them attractive hosts for the heterologous production of commercially valuable enzymes (26,27).…”