Draft Genome Sequence of Escherichia coli Strain VKPM B-10182, Producing the Enzyme for Synthesis of Cephalosporin Acids

Mardanov, Andrey V.; Eldarov, M. A.; Sklyarenko, A. V.; Думина, М. В.; Beletsky, Alexey V.; Yarotsky, S. V.; Ravin, Nikolai V.

doi:10.1128/genomea.01222-14

Cited by 1 publication

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“…It turned out that, in HY strains, the target BGCs are upregulated tens to hundreds of times compared to the original natural isolates [42,43]. Moreover, BGC duplications were observed in some HY strains, whereas no increase in gene dosage occurred in others [42,156,[335][336][337][338][339]. It has been shown that target production does not have a linear correlation with the BGC copy number [340], suggesting that some other modification is also important [88].…”

Section: Key Molecular Events Leading To High-yield Production Of Sec...mentioning

confidence: 99%

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

Zhgun

2023

Fermentation

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The natural fermentation of antibiotics, along with semi-synthetic and synthetic approaches, is one of the most important methods for their production. The majority of the antibiotic market comes from the fermentation of high-yielding (HY) fungal strains. These strains have been obtained since the 1950s from wild-type (WT) isolates as a result of classical strain improvement (CSI) programs primarily involving multi-round random mutagenesis and screening. However, the molecular basis leading to high-yield production was unknown. In recent years, due to the application of multiomic approaches, key changes that occur in CSI programs, with WT strains that become HY industrial producers of a particular antibiotic, have begun to be understood. It becomes obvious that, during CSI, certain universal events are selected, which lead both to a direct increase in the production of the target metabolite and affect other vital processes of the cell (side mutations). These key events include: the upregulation of the target biosynthetic gene cluster (BGC), changes in the system of global regulation, disruption of alternative BGCs, the rearrangement of energy fluxes in favor of the target SM (secondary metabolite), changes in the regulation of the response to stress, and the redirection of primary metabolic pathways to obtain more precursors for target production. This knowledge opens up the possibility of both introducing targeted changes using genetic engineering methods when creating new producers and increasing the production of CSI strains as a result of fermentation with low-molecular compounds, targeted to compensate for the effects of side mutations.

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Section: Key Molecular Events Leading To High-yield Production Of Sec...mentioning

confidence: 99%

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

Zhgun

2023

Fermentation

View full text Add to dashboard Cite

show abstract

Draft Genome Sequence of Escherichia coli Strain VKPM B-10182, Producing the Enzyme for Synthesis of Cephalosporin Acids

Cited by 1 publication

References 5 publications

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

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