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Lantibiotics are lanthionine ring containing natural products that belong to the class of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Recent expansion in the availability of microbial genome data and in silico analysis tools have accelerated the discovery of these promising alternatives to antibiotics. Following the genome‐mining approach, a biosynthetic gene cluster for a putative two‐component lantibiotic, roseocin, was identified in the genome of an Actinomycete, Streptomyces roseosporus NRRL 11379. Posttranslationally modified lanthipeptides of this cluster were obtained by heterologous expression of the genes in Escherichia coli, and were in vitro reconstituted to their bioactive form by exploiting commercial proteases like endoproteinase GluC, and proteinase K. The two peptides displayed synergistic antimicrobial activity against Gram‐positive bacteria including the WHO high‐priority pathogens, MRSA and VRE. Structural characterization confirmed the installation of four (methyl)lanthionine rings with an indispensable disulfide bond in the α‐peptide, and six (methyl)lanthionine rings in the β‐peptide, by a single promiscuous lanthionine synthetase, RosM. Roseocin is the first two‐component lantibiotic from a non‐Firmicute, with extensive lanthionine bridging. [ABSTRACT FROM AUTHOR]

Epoxide hydrolases (EHs; 3.3.2.x) catalyze the enantioselective ring opening of racemic epoxides to the corresponding enantiopure vicinal diols and remaining equivalent unreacted epoxides. These epoxides and diols are used for the synthesis of chiral drug intermediates. With an upsurge in the methods for identification of novel microbial EHs, a lot of EHs have been discovered and utilized for kinetic resolution of racemic epoxides. However, there is still a constraint on the account of limited EHs being successfully applied on the preparative scale for industrial biotransformations. This limitation has to be overcome before application of identified functional EHs on large scale. Many strategies such as optimizing reaction media, immobilizing EHs and laboratory-scale directed evolution of EHs have been adopted for enhancing the industrial potential of EHs. In this review, these approaches have been highlighted which can serve as a pathway for the enrichment of already identified EHs for their application on an industrial scale in future studies. [ABSTRACT FROM AUTHOR]

Background: Frequent use of antibiotics has led to the emergence of antibiotic resistance in bacteria. Lantibiotic compounds are ribosomally synthesized antimicrobial peptides against which bacteria are not able to produce resistance, hence making them a good alternative to antibiotics. Nisin is the oldest and the most widely used lantibiotic, in food preservation, without having developed any significant resistance against it. Having their antimicrobial potential and a limited number, there is a need to identify novel lantibiotics. Methodology/Findings: Identification of novel lantibiotic biosynthetic clusters from an ever increasing database of bacterial genomes, can provide a major lead in this direction. In order to achieve this, a strategy was adopted to identify novel lantibiotic biosynthetic clusters by screening the sequenced genomes for LanT homolog, which is a conserved lantibiotic transporter specific to type IB clusters. This strategy resulted in identification of 54 bacterial strains containing the LanT homologs, which are not the known lantibiotic producers. Of these, 24 strains were subjected to a detailed bioinformatic analysis to identify genes encoding for precursor peptides, modification enzyme, immunity and quorum sensing proteins. Eight clusters having two LanM determinants, similar to haloduracin and lichenicidin were identified, along with 13 clusters having a single LanM determinant as in mersacidin biosynthetic cluster. Besides these, orphan LanT homologs were also identified which might be associated with novel bacteriocins, encoded somewhere else in the genome. Three identified gene clusters had a C39 domain containing LanT transporter, associated with the LanBC proteins and double glycine type precursor peptides, the only known example of such a cluster is that of salivaricin. Conclusion: This study led to the identification of 8 novel putative two-component lantibiotic clusters along with 13 having a single LanM and 3 with LanBC genes. Putative lantibiotic clusters identified here hold the potential for the discovery of novel lantibiotic(s). [ABSTRACT FROM AUTHOR]

In Salmonella enterica serovar Typhimurium, gmk encodes guanylate kinase, an essential enzyme involved in the synthesis and salvage of guanine nucleotides. Here we report the isolation of a mutation in gmk that results in a nutritional requirement for adenine at low temperature. Comparisons of kinetic parameters from the wild-type and mutant Gmk enzymes revealed that the mutant enzyme had a more than 20-fold-higher K[sub m] for ATP than the wild-type enzyme. The growth dependence of the mutant on temperature and/or adenine could not be explained as a direct result of this kinetic difference. We propose a model in which previously described regulatory effects of GMP are responsible for these phenotypes. [ABSTRACT FROM AUTHOR]

Investigates the role of adenosine triphosphate (ATP)-dependent L-cysteine in mycothiol (MSH) biosynthetic pathway. Production of MSH by actinomycetes; Properties of MSH; Importance of MSH in bacterial protection against oxidative stress.

In isoprenoid metabolism, cyclisation is the important gateway to chemical diversity. Terpene synthase is responsible for the cyclisation of a few universal substrates forming hundreds of often stereo-chemically complex mono- and poly-cyclic terpene hydrocarbons with a broad spectrum of functions in pharmaceuticals, flavours and fragrance industry. Although they are discovered and characterised mainly from plants and fungi, yet only a small share of bacterial terpenes has been investigated so far owing to their low level of expression in wild-type microorganisms. Extensive bacterial genome mining has revealed a treasure trove of terpene synthase genes and their regulated heterologous overexpression has pitched-in to describe the biochemical function of putative genes and sequester new terpene metabolites. This review deals with the modern genome mining techniques and molecular methods, providing more experimental tools for studying the structure and functions of terpenoid metabolites and strongly supports the idea that genome mining is a utile approach in deciphering the terpenoid diversity in bacteria. [ABSTRACT FROM AUTHOR]