title: Aggregation of germlings is a major contributing factor towards mycelial heterogeneity of Streptomyces.
abstract: Streptomycetes are filamentous bacteria that produce numerous valuable compounds, including the majority of clinically used antibiotics. At an industrial scale, most of these compounds are produced in bioreactors. Growth of streptomycetes under these conditions is characterized by the formation of complex mycelial particles, whose sizes follow a bimodal distribution. Given the correlation between specific productivity and morphology, this size heterogeneity poses a potential drawback in industry. Recent work indicates that mycelial morphology is controlled by a number of genes that encode proteins required for the synthesis of cell surface-associated glycans. Using a quantifiable system based on fluorescent markers, we here show that these glycans mediate aggregation between germlings and young mycelia, yielding mycelial particles that originate from many different individuals. We also demonstrate that at later time points aggregation between distinct particles is no longer detectable. Notably, the absence of the corresponding glycan synthases yields mycelia that are homogeneous in size, identifying mycelial aggregation as a driving factor towards size heterogeneity. Given that aggregation is widespread within streptomycetes and can also occur between different Streptomyces strains, our work paves the way to improve Streptomyces as a cell factory for the production of known metabolites, but possibly also to discover new ones.
authors.affiliation: Microbial Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.
authors.forename: Boris
authors.initials: B
authors.lastname: Zacchetti
authors.affiliation: Microbial Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Willemse
authors.affiliation: Microbiology, Department of Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Brand
authors.initials: B
authors.lastname: Recter
authors.affiliation: Microbial Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.
authors.forename: Dino
authors.initials: D
authors.lastname: van Dissel
authors.affiliation: Microbial Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.
authors.forename: Gilles P
authors.initials: GP
authors.lastname: van Wezel
authors.affiliation: Microbiology, Department of Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: H A B
authors.initials: HA
authors.lastname: Wösten
authors.affiliation: Microbial Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: Claessen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D019149:Bioreactors; D005285:Fermentation; D005427:Flocculation; D017353:Gene Deletion; D015870:Gene Expression; D017930:Genes, Reporter; D018740:Genetic Heterogeneity; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007218:Industrial Microbiology / Q000379:methods*; D008025:Ligases / Q000172:deficiency* / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D060847:Metabolic Engineering; D025282:Mycelium / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D000097573:Red Fluorescent Protein
chemical_list: D001426:Bacterial Proteins; D049452:Green Fluorescent Proteins; D008025:Ligases; D008164:Luminescent Proteins; D011135:Polysaccharides, Bacterial; D000097573:Red Fluorescent Protein; C485184:enhanced green fluorescent protein