Summary: S treptomyces albus J 1074 is a streptomycete strain widely used as a host for expression of secondary metabolite gene clusters. Bioinformatic analysis of the genome of this organism predicts the presence of 27 gene clusters for secondary metabolites. We have used three different strategies for the activation of some of these silent/cryptic gene clusters in S . albus J 1074: two hybrid polyketide‐non‐ribosomal peptides ( PK‐NRP ) (antimycin and 6‐ epi ‐alteramides), a type I PK (candicidin), a non‐ribosomal peptides ( NRP ) (indigoidine) and glycosylated compounds (paulomycins). By insertion of a strong and constitutive promoter in front of selected genes of two clusters, production of the blue pigment indigoidine and of two novel members of the polycyclic tetramate macrolactam family (6‐ epi ‐alteramides A and B ) was activated. Overexpression of positive regulatory genes from the same organism also activated the biosynthesis of 6‐ epi ‐alteramides and heterologous expression of the regulatory gene pim M of the pimaricin cluster activated the simultaneous production of candicidins and antimycins, suggesting some kind of cross‐regulation between both clusters. A cluster for glycosylated compounds (paulomycins) was also identified by comparison of the high‐performance liquid chromatography profiles of the wild‐type strain with that of a mutant in which two key enzymes of the cluster were simultaneously deleted.

This review highlights the main genetic features of circular bacteriocins, which require the co-ordinated expression of several genetic determinants

Abstract:  Melatonin (N‐acetyl‐5‐methoxytryptamine) is an indoleamine with a range of antioxidative properties. Melatonin is endogenously produced in the eye and in other organs. Current evidence suggests that melatonin may act as a protective agent in ocular conditions such as photo‐keratitis, cataract, glaucoma, retinopathy of prematurity and ischemia/reperfusion injury. These diseases are sight‐threatening and they currently remain, for the most part, untreatable. The pathogenesis of these conditions is not entirely clear but oxidative stress has been proposed as one of the causative factors. Elevated levels of various reactive oxygen and nitrogen species have been identified in diseased ocular structures. These reactants damage the structure and deplete the eye of natural defense systems, such as the antioxidant, reduced glutathione, and the antioxidant enzyme superoxide dismutase. Oxidative damage in the eye leads to apoptotic degeneration of retinal neurons and fluid accumulation. Retinal degeneration decreases visual sensitivity and even a small change in the fluid content of the cornea and crystalline lens is sufficient to disrupt ocular transparency. In the eye, melatonin is produced in the retina and in the ciliary body. Continuous regeneration of melatonin in the eye offers a frontier antioxidative defense for both the anterior and posterior eye. However, melatonin production is minimal in newborns and its production gradually wanes in aging individuals as indicated by the large drop in circulating blood concentrations of the indoleamine. These individuals are possibly at risk of contracting degenerative eye diseases that are free radical‐based. Supplementation with melatonin, a potent antioxidant, in especially the aged population should be considered as a prophylaxis to preserve visual functions. It may benefit many individuals worldwide, especially in countries where access to medical facilities is limited.