Methodologies and Strategies for the Bioengineering of Lantibiotics

Nagao, Jun Ichi; Nishie, Mami; Sonomoto, Kenji

doi:10.2174/138920111796117355

Cited by 8 publications

(6 citation statements)

References 64 publications

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“…The term lanthipeptides is a relatively new name for the group of peptide antibiotics formerly called lantibiotics (4). The name needed updating given that some of these peptides were found to not have antibacterial activity (5).…”

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confidence: 99%

“…The name needed updating given that some of these peptides were found to not have antibacterial activity (5). Lanthipeptides are ribosomally synthesized, containing a leader peptide that is cleaved off by a protease and a core peptide that is responsible for the bioactivity (4). Particular features of lanthipeptides, such as their novel and diverse mechanisms of action and the difficulty for sensitive bacteria to acquire resistance, have aroused considerable interest in these molecules as potential therapeutic agents (3,6).…”

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confidence: 99%

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Site-Directed Mutations in the Lanthipeptide Mutacin 1140

Chen

Wilson-Stanford

Cromwell

et al. 2013

Appl Environ Microbiol

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The oral bacterium Streptococcus mutans, strain JH1140, produces the antibiotic mutacin 1140. Mutacin 1140 belongs to a group of antibiotics called lanthipeptides. More specifically, mutacin 1140 is related to the epidermin type A(I) lanthipeptides. Mutagenesis experiments of this group of lanthipeptides have been primarily restricted to the posttranslationally modified mesolanthionine and 3-methyllanthionine residues. Site-directed mutagenesis of the core peptide of mutacin 1140 was performed using the suicide vector pVA891. Substitutions of the N-terminal residue, the charged residue in the hinge region, and residues in ring A and intertwined rings C and D were investigated. A truncation and insertion of residues in ring A and intertwined rings C and D were also performed to determine whether or not they would alter the antimicrobial activity of the producing strain. Bioassays revealed that five of 14 mutants studied had improved antimicrobial activity against the indicator strain Micrococcus luteus ATCC 10240. MICs against Streptococcus mutans UA159, Streptococcus pneumoniae ATCC 27336, Staphylococcus aureus ATCC 25923, Clostridium difficile UK1, and Micrococcus luteus ATCC 10240 were determined for three mutacin 1140 variants that had the most significant increases in bioactivity in the M. luteus bioassay. This mutagenesis study of the epidermin group of lanthipeptides shows that antimicrobial activity can be significantly improved.

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confidence: 99%

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confidence: 99%

Site-Directed Mutations in the Lanthipeptide Mutacin 1140

Chen

Wilson-Stanford

Cromwell

et al. 2013

Appl Environ Microbiol

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“…Pseudomycoicidin), recombinant fusion bacteriocins (e.g. sonorensin) and new expression system, but studies were centred on the improvement of the expression level via enhancement of mRNA stability as well as to understand the correlation of their molecular structure and biological activity (Nagao et al 2011). Genes involved in the production of the mature (active) peptide can be identified and cloned due to their ribosomal synthesis feature.…”

Section: Bioengineeringmentioning

confidence: 99%

“…However, analysis of their stability and productivity at large scale (e.g. in bioreactor) are rarely exploited (Nagao et al 2011;Basi-Chipalu et al 2015). In a study, high homologous expression of thuricin H has been successfully developed using newly constructed expression vector pGW133 on the basis of the E. coli-B.…”

Section: Bioengineeringmentioning

confidence: 99%

Biomanufacturing process for the production of bacteriocins from Bacillaceae family

Lajis

2020

Bioresour. Bioprocess.

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Members of Bacillaceae family are of major interest in medical industry due to vast antimicrobial peptides they produce as therapeutic agents. For decades, synthetic and natural occurring antibiotics have been used to treat infectious diseases, but heavy dependence on these drugs has led to significant drawbacks which propel continuous development of new antibiotics generation. Recent findings have shown several bacteriocins of Bacillaceae as promising alternatives to the conventional drugs to combat the emergence of new drug-resistant pathogens. In this present review, Bacillaceae bacteriocins' classification such as lantibiotics and thiazole/oxazole-modified microcins as well as their biochemical characterization such as sensitivity to enzymes, temperature, pH and chemicals are described. This article enlightens on the medical application of several Bacillaceae bacteriocins emphasizing those that underwent and ongoing preclinical trials. This review also discusses the development of Bacillaceae bacteriocins production, focusing strains selection and fermentation factors such as inocula size, medium (carbon, nitrogen, minerals sources), temperature, pH, agitation and aeration rate, dissolved oxygen tension (DOT), fermentation time, inducers and mode of operation via various statistical methods for their optimization. It also highlights recent advance in the production of bioengineered and recombinant bacteriocins in bioreactors system which are rarely disclosed in literature.

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“…Mainly three different strategies have been utilized to produce novel lantibiotics through engineering. i) In vivo engineering involves creating lantibiotic variants that have increased activity by manipulating the biosynthetic gene cluster [37,38]. This strategy can also help engineer lantibioticproducing strains of bacteria to synthesize significantly more antibiotic [39][40][41].…”

Section: Introductionmentioning

confidence: 99%