Strain Improvement and Strain Maintenance Revisited. The Use of Actinoplanes teichomyceticus ATCC 31121 Protoplasts in the Identification of Candidates for Enhanced Teicoplanin Production

Multicellular cooperation in actinomycetes is a division of labor-based beneficial trait where phenotypically specialized clonal subpopulations, or genetically distinct lineages, perform complementary tasks. The division of labor improves the access to nutrients and optimizes reproductive and vegetative tasks while reducing the costly production of secondary metabolites and/or of secreted enzymes. In this study, we took advantage of the possibility to isolate genetically distinct lineages deriving from the division of labor, for the isolation of heterogeneous teicoplanin producer phenotypes from Actinoplanes teichomyceticus ATCC 31121. In order to efficiently separate phenotypes and associated genomes, we produced and regenerated protoplasts. This approach turned out to be a rapid and effective strain improvement method, as it allowed the identification of those phenotypes in the population that produced higher teicoplanin amounts. Interestingly, a heterogeneous teicoplanin complex productivity pattern was also identified among the clones. This study suggests that strain improvement and strain maintenance should be integrated with the use of protoplasts as a strategy to unravel the hidden industrial potential of vegetative mycelium.

Draft Genome Sequence of Teicoplanin-Producing Strain Actinoplanes teichomyceticus CPCC 203265

We report here the draft genome sequence of Actinoplanes teichomyceticus CPCC 203265, a producer of glycopeptide antibiotic teicoplanin, which has significant inhibitory activity against multidrug-resistant Gram-positive pathogens. The draft genome size is 8 Mb, with a G+C content of 72.8%, and its sequence will facilitate the genome exploration of novel secondary metabolites.

Crystal structure of TchmY from Actinoplanes teichomyceticus

Moenomycin-type antibiotics are phosphoglycolipids that are notable for their unique modes of action and have proven to be useful in animal nutrition. The gene clusters tchm from Actinoplanes teichomyceticus and moe from Streptomyces are among a limited number of known moenomycin-biosynthetic pathways. Most genes in tchm have counterparts in the moe cluster, except for tchmy and tchmz, the functions of which remain unknown. Sequence analysis indicates that TchmY belongs to the isoprenoid enzyme C2-like superfamily and may serve as a prenylcyclase. The enzyme was proposed to be involved in terminal cyclization of the moenocinyl chain in teichomycin, leading to the diumycinol chain of moenomycin isomers. Here, recombinant TchmY protein was expressed in Escherichia coli and its crystal structure was solved by SIRAS. Structural analysis and comparison with other prenylcyclases were performed. The overall fold of TchmY consists of an (α/α)6-barrel, and a potential substrate-binding pocket is found in the central chamber. These results should provide important information regarding the biosynthetic basis of moenomycin antibiotics.