Morphogenesis of Streptomyces in submerged cultures

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.