Abstract
BackgroundStreptomycetes produce a plethora of natural products including antibiotics and anticancer drugs, as well as many industrial enzymes. Their mycelial life style is a major bottleneck for industrial exploitation and over decades strain improvement programs have selected production strains with better growth properties. Uncovering the nature of the underlying mutations should allow the ready transfer of desirable traits to other production hosts.ResultsHere we report that the mat gene cluster, which was identified through reverse engineering of a non-pelleting mutant selected in a chemostat, is key to pellet formation of Streptomyces lividans. Deletion of matA or matB, which encode putative polysaccharide synthases, effects mycelial metamorphosis, with very small and open mycelia. Growth rate and productivity of the matAB null mutant were increased by over 60% as compared to the wild-type strain.ConclusionHere, we present a way to counteract pellet formation by streptomycetes, which is one of the major bottlenecks in their industrial application. The mat locus is an ideal target for rational strain design approaches aimed at improving streptomycetes as industrial production hosts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-015-0224-6) contains supplementary material, which is available to authorized users.
Highlights
Streptomycetes produce a plethora of natural products including antibiotics and anticancer drugs, as well as many industrial enzymes
Derivatives of S. lividans 66 with improved growth characteristics Many Streptomyces species produce large mycelial clumps when grown in liquid media, which is a disadvantage for industrial application as it is associated with slow growth and poor nutrient utilization
In an attempt to obtain faster growth with less dense pellets, a nonpelleting derivative of S. lividans 66 was obtained previously through growth of some 100 generations in continuous culture at a medium dilution rate, called PM02, while a strain with an intermediate phenotype was obtained after 70 generations, called PM01, which grows as small loosely packed mycelial pellets (Figure 1)
Summary
Streptomycetes produce a plethora of natural products including antibiotics and anticancer drugs, as well as many industrial enzymes Their mycelial life style is a major bottleneck for industrial exploitation and over decades strain improvement programs have selected production strains with better growth properties. As surface-grown cultures, streptomycetes exhibit a complex multicellular life cycle [3] This starts with a single spore that germinates to form vegetative hyphae, which grow out following a process of hyphal growth and branching to produce a branched vegetative mycelium [4]. Directed mutagenesis should result in fewer additional mutations and the changes can be transferred from one strain to another [15] The latter is of particular importance for Streptomyces, where secondary metabolites cannot be moved to generally preferred production host such as E. coli or B. subtilis
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