In Saccharopolyspora erythraea, the genes that govern synthesis of the polyketide portion of the macrolide antibiotic erythromycin are organized in six repeated units that encode fatty acid synthase (FAS)-like activities. Each repeated unit is designated a module, and two modules are contained in a single open reading frame. A model for the synthesis of this complex polyketide is proposed, where each module encodes a functional synthase unit and each synthase unit participates specifically in one of the six FAS-like elongation steps required for formation of the polyketide. In addition, genetic organization and biochemical order of events appear to be colinear. Evidence for the model is provided by construction of a selected mutant and by isolation of a polyketide of predicted structure.

https://science.sciencemag.org/content/sci/252/5006/675.full.pdf

Modular organization of genes required for complex polyketide biosynthesis.

The lantibiotics are a group of ribosomally synthesised, post-translationally modified peptides containing unusual amino acids, such as dehydrated and lanthionine residues. This group of bacteriocins has attracted much attention in recent years due to the success of the well characterised lantibiotic, nisin, as a food preservative. Numerous other lantibiotics have since been identified and can be divided into two groups on the basis of their structures, designated type-A and type-B. To date, many of these lantibiotics have undergone extensive characterisation resulting in an advanced understanding of them at both the structural and mechanistic level. This review outlines some of the more recent developments in the biochemistry, genetics and mechanism of action of these peptides.

Lantibiotics: structure, biosynthesis and mode of action

Publisher Summary The chapter focuses on mycological aspects of the genus Metarhizium . The genus includes several species, varieties within species, and individual isolates with broad ranges of physiological traits—including host range. The interactions of these fungi with their hosts, and the large literature on their use for pest control, largely define the scientific and popular concepts of Metarhizium spp. Fungi of the hyphomycete genus Metarhizium have been isolated from infected insects and soil. Although some isolates of these fungi have rather restricted host ranges, the group is better known for its ability to kill a wide spectrum of insects, including insects in at least seven orders. The common name for Metarhizium -induced disease is “green muscardine,” based on the encrustation of insect cadavers with green conidia. The rapid increase in research on Metarhizium , followed by sustained high scientific output, can be explained by several important worldwide attitude changes and the initiation of several promising Metarhizium -based pest-control and molecular-biology efforts.

Metarhizium spp., cosmopolitan insect-pathogenic fungi: mycological aspects.

Microbial surfactants are a structurally diverse group of compounds consisting of hydrophilic and hydrophobic domains and which partition preferentially at interfaces. Biosurfactants are of increasing interest commercially as substitutes for synthetic surfactants particularly for environmental applications. This article discusses recent progress in the genetic and biochemical analysis of biosurfactant synthesis as well as the current status of fermentation technologies.

Surface-active compounds from microorganisms.

Nisin is a small gene-encoded antimicrobial protein produced by Lactococcus lactis that contains unusual dehydroalanine and dehydrobutyrine residues. The reactivity of these residues toward nucleophiles was explored by reacting nisin with a variety of mercaptans. The kinetics of reaction with 2-mercaptoethane-sulfonate and thioglycolate indicated that the reaction pathway includes a binding step. Reaction of nisin at high pH resulted in the formation of multimeric products, apparently as a result of intramolecular and intermolecular reactions between nucleophilic groups and the dehydro residues. One of the nucleophiles had a pKa of about 9.8. The unique vinyl protons of the dehydro residues that give readily identifiable proton nuclear magnetic resonances were used to observe the addition of nucleophiles to the dehydro moiety. After reaction with nucleophiles, nisin lost its antibiotic activity and no longer showed the dehydro resonances, indicating that the dehydro groups had been modified. The effect of pH on the solubility of nisin was determined; the solubility was quite high at low pH (57 mg/ml at pH 2) and was much lower at high pH (0.25 mg/ml at pH 8 to 12), as measured before significant pH-induced chemical modification had occurred. High-performance liquid chromatography on a C18 column was an effective technique for separating unmodified nisin from its reaction products. The cyanogen bromide cleavage products of nisin were about 90% less active toward inhibition of bacterial spore outgrowth than was native nisin. These results are consistent with earlier observations, which suggested that the dehydro residues of nisin have a role in the mechanism of antibiotic action, in which they act as electrophilic Michael acceptors toward nucleophiles in the cellular target.

H von Döhren

Papers

Biosynthesis of Peptide Antibiotics