Streptomyces are filamentous soil bacteria that produce more than half of the known microbial antibiotics. We present the first genome-scale metabolic model of a representative of this group-Streptomyces coelicolor A3(2). The metabolism reconstruction was based on annotated genes, physiological and biochemical information. The stoichiometric model includes 819 biochemical conversions and 152 transport reactions, accounting for a total of 971 reactions. Of the reactions in the network, 700 are unique, while the rest are iso-reactions. The network comprises 500 metabolites. A total of 711 open reading frames (ORFs) were included in the model, which corresponds to 13% of the ORFs with assigned function in the S. coelicolor A3(2) genome. In a comparative analysis with the Streptomyces avermitilis genome, we showed that the metabolic genes are highly conserved between these species and therefore the model is suitable for use with other Streptomycetes. Flux balance analysis was applied for studies of the reconstructed metabolic network and to assess its metabolic capabilities for growth and polyketides production. The model predictions of wild-type and mutants' growth on different carbon and nitrogen sources agreed with the experimental data in most cases. We estimated the impact of each reaction knockout on the growth of the in silico strain on 62 carbon sources and two nitrogen sources, thereby identifying the "core" of the essential reactions. We also illustrated how reconstruction of a metabolic network at the genome level can be used to fill gaps in genome annotation.

Filamentous actinomycetes are commercially widely used as producers of natural products (in particular antibiotics) and of industrial enzymes. However, the mycelial lifestyle of actinomycetes, resulting in highly viscous broths and unfavorable pellet formation, has been a major bottleneck in their commercialization. Here we describe the successful morphological engineering of industrially important streptomycetes through controlled expression of the morphogene ssgA. This led to improved growth of many industrial and reference streptomycetes, with fragmentation of the mycelial clumps resulting in significantly enhanced growth rates in batch fermentations of Streptomyces coelicolor and Streptomyces lividans. Product formation was also stimulated, with a twofold increase in yield of enzyme production by S. lividans. We anticipate that the use of the presented methodology will make actinomycetes significantly more attractive as industrial and sustainable production hosts.

The spores of Penicillium chrysogenum are of the noncoagulating type, and after spore germination a culture of disperse mycelia is obtained. In this study, it is shown that when the hyphal elements increase in size, they may agglomerate, and depending on the operating conditions, these agglomerates may develop into pellets with a dense core. The influence of initial spore concentration and agitation rate on agglomeration, leading to pellet formation, was studied. For a low concentration of spores in the inoculum, only a few hyphal elements agglomerate and pellets with a small diameter are obtained. At higher spore concentrations, many hyphal elements agglomerate and develop into large diameter pellets. Finally, at a very high spore concentration in the inoculum, the final hyphal element size is small and agglomerates therefore are not formed. With a high agitation rate, the agglomeration of hyphal elements is reduced. In a repeated fed-batch cultivation, where there was a shift from pellet morphology to disperse mycelia, it was found that there is no relation between macroscopic morphology and penicillin production by P. chrysogenum. The morphology was quantified throughout the repeated fed-batch cultivation, and both the pellet diameter and the concentration of pellets were affected by the agitation rate.

BackgroundMicrobial formation of acetone, isopropanol, and butanol is largely restricted to bacteria belonging to the genus Clostridium. This ability has been industrially exploited over the last 100 years. The solvents are important feedstocks for the chemical and biofuel industry. However, biological synthesis suffers from high substrate costs and competition from chemical synthesis supported by the low price of crude oil. To render the biotechnological production economically viable again, improvements in microbial and fermentation performance are necessary. However, no comprehensive comparisons of respective species and strains used and their specific abilities exist today.ResultsThe genomes of a total 30 saccharolytic Clostridium strains, representative of the species Clostridium acetobutylicum, C. aurantibutyricum, C. beijerinckii, C. diolis, C. felsineum, C. pasteurianum, C. puniceum, C. roseum, C. saccharobutylicum, and C. saccharoperbutylacetonicum, have been determined; 10 of them completely, and compared to 14 published genomes of other solvent-forming clostridia. Two major groups could be differentiated and several misclassified species were detected.ConclusionsOur findings represent a comprehensive study of phylogeny and taxonomy of clostridial solvent producers that highlights differences in energy conservation mechanisms and substrate utilization between strains, and allow for the first time a direct comparison of sequentially selected industrial strains at the genetic level. Detailed data mining is now possible, supporting the identification of new engineering targets for improved solvent production.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-017-0742-z) contains supplementary material, which is available to authorized users.

A previously derived population model describing the average properties of hyphal elements in submerged cultures of filamentous fungi was revised, and a term for the influence fo spore germination on the average total hyphal length was added. The model was derived from a general balance for the distribution function for the hyphal elements. Based on experimental data and the derived model, simple kinetic expressions for spore germination, tip extension, branching, and hyphal break-up were set up. It is concluded that spore germination can be quantified by three parameters: (1) the time at which spore germination is initiated, (2) the time at which spore germination terminates, and (3) the fraction of viable spores in a spore suspension. The frequency of spore germination can be described with the B-distribution. For growth kinetics it is concluded that the branching frequency is closely correlated with the total hyphal length and that the average tip-extension rate can be described with saturation kinetics with respect to the hyphal length. Finally, the rate of fragmentation is linearly related to the energy input to the bioreactor, and related to the effective hyphal length.