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

Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 24
Author(s):  
Luca Mellere ◽  
Adriana Bava ◽  
Carmine Capozzoli ◽  
Paola Branduardi ◽  
Francesca Berini ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Division Of Labor ◽  
Effective Strain ◽  
Strain Improvement ◽  
Vegetative Mycelium ◽  
Actinoplanes Teichomyceticus ◽  
Improvement Method ◽  
Secreted Enzymes ◽  
Productivity Pattern

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.

Microbial Synthesis of Secondary Metabolites and Strain Improvement

2018 ◽  
pp. 75-90
Author(s):  
Sergio Sánchez ◽  
Beatriz Ruiz-Villafán ◽  
Corina D. Ceapa ◽  
A.L. Demain
Keyword(s):  
Secondary Metabolites ◽  
Strain Improvement ◽  
Microbial Synthesis

scholarly journals An Insight into the “-Omics” Based Engineering of Streptomycetes for Secondary Metabolite Overproduction

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Amit Kumar Chaudhary ◽  
Dipesh Dhakal ◽  
Jae Kyung Sohng
Keyword(s):  
Secondary Metabolites ◽  
Biological Activities ◽  
Genetic Material ◽  
Strain Improvement ◽  
Culture Conditions ◽  
Strain Development ◽  
Recent Advancement ◽  
Chemical Factory ◽  
Insight Into ◽  
Selection Of

Microorganisms produce a range of chemical substances representing a vast diversity of fascinating molecular architectures not available in any other system. Among them,Streptomycesare frequently used to produce useful enzymes and a wide variety of secondary metabolites with potential biological activities.Streptomycesare preferred over other microorganisms for producing more than half of the clinically useful naturally originating pharmaceuticals. However, these compounds are usually produced in very low amounts (or not at all) under typical laboratory conditions. Despite the superiority ofStreptomyces, they still lack well documented genetic information and a large number of in-depth molecular biological tools for strain improvement. Previous attempts to produce high yielding strains required selection of the genetic material through classical mutagenesis for commercial production of secondary metabolites, optimizing culture conditions, and random selection. However, a profound effect on the strategy for strain development has occurred with the recent advancement of whole-genome sequencing, systems biology, and genetic engineering. In this review, we demonstrate a few of the major issues related to the potential of “-omics” technology (genomics, transcriptomics, proteomics, and metabolomics) for improving streptomycetes as an intelligent chemical factory for enhancing the production of useful bioactive compounds.

Targeting the Osmotic Stress Response for Strain Improvement of an Industrial Producer of Secondary Metabolites

2015 ◽  
Vol 25 (11) ◽  
pp. 1787-1795 ◽  
Author(s):  
Octavio Godinez ◽  
Paul Dyson ◽  
Ricardo del Sol ◽  
Javier Barrios-Gonzalez ◽  
Cesar Millan-Pacheco ◽  
...  
Keyword(s):  
Stress Response ◽  
Secondary Metabolites ◽  
Osmotic Stress ◽  
Strain Improvement ◽  
Osmotic Stress Response

scholarly journals Insight into the Genome of Diverse Penicillium chrysogenum Strains: Specific Genes, Cluster Duplications and DNA Fragment Translocations

2020 ◽  
Vol 21 (11) ◽  
pp. 3936
Author(s):  
Juan F. Martín
Keyword(s):  
Secondary Metabolites ◽  
Gene Cluster ◽  
Penicillium Chrysogenum ◽  
Tandem Repeats ◽  
Treatment Plant ◽  
Strain Improvement ◽  
Pulse Field ◽  
Wild Type ◽  
Improvement Programs ◽  
Dna Fragment

Background: There are eighteen species within the Penicillium genus section chrysogena, including the original penicillin producers Penicillium notatum (Fleming strain) and Penicillium chrysogenum NRRL 1951. Other wild type isolates of the Penicillium genus are relevant for the production of useful proteins and primary or secondary metabolites. The aim of this article is to characterize strain specific genes and those genes which are involved in secondary metabolite biosynthesis, particularly the mutations that have been introduced during the β-lactams strain improvement programs. Results: The available genomes of several classical and novel P. chrysogenum strains have been compared. The first genome sequenced was that of the reference strain P. chrysogenum Wis54-1255, which derives from the wild type P. chrysogenum NRRL 1951; its genome size is 32.19 Mb and it encodes 12,943 proteins. Four chromosomes were resolved in P. chrysogenum and P. notatum by pulse field gel electrophoresis. The genomes of three industrial strains have a similar size but contain gene duplications and truncations; the penicillin gene cluster copy number ranges from one in the wild type to twelve in the P. chrysogenum ASP-E1 industrial strain and is organized in head to tail tandem repeats. The genomes of two new strains, P. chrysogenum KF-25, a producer of antifungal proteins isolated from a soil sample, and P. chrysogenum HKF2, a strain with carbohydrate-converting activities isolated from a sludge treatment plant, showed strain specific genes. Conclusions: The overall comparison of all available P. chrysogenum genomes indicates that there are a significant number of strain-specific genes, mutations of structural and regulatory genes, gene cluster duplications and DNA fragment translocations. This information provides important leads to improve the biosynthesis of enzymes, antifungal agents, prebiotics or different types of secondary metabolites.

scholarly journals Harnessing the yeast Saccharomyces cerevisiae for the production of fungal secondary metabolites

2021 ◽  
Author(s):  
Guokun Wang ◽  
Douglas B. Kell ◽  
Irina Borodina
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Secondary Metabolites ◽  
High Throughput Screening ◽  
Large Scale ◽  
Strain Improvement ◽  
Cell Factory ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cell Factories ◽  
Genetically Engineer ◽  
Fungal Secondary Metabolites

Abstract Fungal secondary metabolites (FSMs) represent a remarkable array of bioactive compounds, with potential applications as pharmaceuticals, nutraceuticals, and agrochemicals. However, these molecules are typically produced only in limited amounts by their native hosts. The native organisms may also be difficult to cultivate and genetically engineer, and some can produce undesirable toxic side-products. Alternatively, recombinant production of fungal bioactives can be engineered into industrial cell factories, such as aspergilli or yeasts, which are well amenable for large-scale manufacturing in submerged fermentations. In this review, we summarize the development of baker’s yeast Saccharomyces cerevisiae to produce compounds derived from filamentous fungi and mushrooms. These compounds mainly include polyketides, terpenoids, and amino acid derivatives. We also describe how native biosynthetic pathways can be combined or expanded to produce novel derivatives and new-to-nature compounds. We describe some new approaches for cell factory engineering, such as genome-scale engineering, biosensor-based high-throughput screening, and machine learning, and how these tools have been applied for S. cerevisiae strain improvement. Finally, we prospect the challenges and solutions in further development of yeast cell factories to more efficiently produce FSMs.

scholarly journals Antibiotic production in Streptomyces is organized by a division of labor through terminal genomic differentiation

2020 ◽  
Vol 6 (3) ◽  
pp. eaay5781 ◽  
Author(s):  
Zheren Zhang ◽  
Chao Du ◽  
Frédérique de Barsy ◽  
Michael Liem ◽  
Apostolos Liakopoulos ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Division Of Labor ◽  
Antibiotic Production ◽  
Streptomyces Coelicolor ◽  
Social Groups ◽  
Cooperative Groups ◽  
Fitness Costs ◽  
Individual Fitness ◽  
Group Members ◽  
Chromosomal Changes

One of the hallmark behaviors of social groups is division of labor, where different group members become specialized to carry out complementary tasks. By dividing labor, cooperative groups increase efficiency, thereby raising group fitness even if these behaviors reduce individual fitness. We find that antibiotic production in colonies of Streptomyces coelicolor is coordinated by a division of labor. We show that S. coelicolor colonies are genetically heterogeneous because of amplifications and deletions to the chromosome. Cells with chromosomal changes produce diversified secondary metabolites and secrete more antibiotics; however, these changes reduced individual fitness, providing evidence for a trade-off between antibiotic production and fitness. Last, we show that colonies containing mixtures of mutants and their parents produce significantly more antibiotics, while colony-wide spore production remains unchanged. By generating specialized mutants that hyper-produce antibiotics, streptomycetes reduce the fitness costs of secreted secondary metabolites while maximizing the yield and diversity of these products.

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

2019 ◽  
Vol 8 (41) ◽  
Author(s):  
Xingxing Li ◽  
Cong Zhang ◽  
Xuan Lei ◽  
Lifei Wang ◽  
Bin Hong
Keyword(s):  
Secondary Metabolites ◽  
Genome Sequence ◽  
Inhibitory Activity ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Draft Genome Sequence ◽  
Its Sequence ◽  
Glycopeptide Antibiotic ◽  
Content Type ◽  
Actinoplanes Teichomyceticus

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.

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