Reducing branching and enhancing fragmentation in culturing filamentous microorganisms

Abstract

The invention relates to the field of microorganisms and in particular to the culturing of microorganisms. The invention provides means and methods for enhancing the culturing properties of filamentous microorganisms, in particular filamentous fungi. The means and methods according to the invention comprise reducing branching and/or enhancing the fragmentation of filamentous microorganisms, whereby their liquid culturing properties are improved. In one embodiment, this is achieved by providing the microorganisms with activity capable of enhancing fragmentation and/or reducing branching, such as the activity in which, e.g., Streptomyces griseus is encoded by ssgA.

1 . A method for producing a filamentous bacterium exhibiting reduced branching and fragment septation during growth, said method comprising: 
 providing a filamentous bacterium, said filamentous bacterium lacking significant endogenous SsgA-activity, with the capability of having or expressing heterologous SsgA-activity, which SsgA-activity, in  Streptomyces griseus , is encoded by an ssgA gene having at least the nucleotide sequence of SEQ ID NO: 1.    
     
     
         2 . A method for producing a filamentous bacterium exhibiting enhanced fragmentation during growth, said method comprising: 
 providing a filamentous bacterium, wherein said filamentous bacterium lacks significant endogenous SsgA-activity, with the capability of having or expressing heterologous SsgA-activity, which SsgA-activity in  Streptomyces griseus  is encoded by an ssgA gene having the nucleotide sequence of SEQ ID NO: 1.    
     
     
         3 . The method according to  claim 1 , wherein said additional SsgA-activity is provided by transfecting or transforming said filamentous bacterium with additional genetic information encoding said additional SsgA-activity.  
     
     
         4 . The method according to  claim 3 , wherein said additional genetic information comprises an ssgA gene or a derivative or fragment thereof encoding similar SsgA-activity.  
     
     
         5 . The method according to  claim 4 , wherein said ssgA gene is derived from an actinomycete or a streptomycete.  
     
     
         6 . The method according to  claim 5 , wherein said gene originates from  Streptomyoes griseus, Streptomyces collinus, Streptomyces albus, Streptomyces goldeniensis  or  Streptomyces netropsis.    
     
     
         7 . The method according to  claim 3 , wherein said additional genetic information is integrated into the filamentous bacterium's genome.  
     
     
         8 . The method according to  claim 3 , wherein said additional genetic information is part of an episomal element.  
     
     
         9 . The method according to  claim 3 , wherein said filamentous bacterium does not have significant endogenous SsgA-activity.  
     
     
         10 . The method according to  claim 3 , wherein said SsgA-activity is inducible or repressible with a signal.  
     
     
         11 . The method according to  claim 3 , wherein said filamentous bacterium is an  Actinomyces  or  Streptomyces.    
     
     
         12 . The method according to  claim 3 , wherein said filamentous bacterium produces an antibiotic or a protein.  
     
     
         13 . The method according to  claim 12 , wherein said protein is heterologous to said filamentous bacterium.  
     
     
         14 . The method according to  claim 12 , wherein said protein is expressed from a vector encoding said protein present in said filamentous bacterium.  
     
     
         15 . The method according to  claim 14 , wherein said protein is secreted by said filamentous bacterium.  
     
     
         16 . A filamentous bacterium produced by the method according  claim 3 .  
     
     
         17 . The filamentous bacterium of  claim 16 , wherein said filamentous bacterium is an actinomycete.  
     
     
         18 . A method for producing an antibiotic or a useful protein comprising culturing the filamentous bacterium according to  claim 15  in a culture and harvesting said antibiotic or protein from said culture.  
     
     
         19 . The method according to  claim 18 , wherein said culturing is submerged culture.  
     
     
         20 . The method according to  claim 2 , wherein said additional SsgA-activity is provided by transfecting or transforming said filamentous bacterium with additional genetic information encoding said additional SsgA-activity.  
     
     
         21 . The method according to  claim 20 , wherein said additional genetic information comprises an ssgA gene.  
     
     
         22 . The method according to  claim 21 , wherein said ssgA gene originates from an actinomycete.  
     
     
         23 . The method according to  claim 21 , wherein said ssgA gene originates from a streptomycete.  
     
     
         24 . The method according to  claim 23 , wherein said gene is derived from  Streptomyoes griseus, Streptomyces collinus, Streptomyces albus, Streptomyces goldeniensis  or  Streptomyces netropsis.