Reconstruction of larval origins based on genetic relatedness and biophysical modeling.

The assessment of the mechanisms and patterns of larval connectivity between geographically separated populations leads to a better understanding of benthic marine population dynamics, especially in commercially valuable species. This study investigated for the first time the fine-scale temporal genetic variability of new settlers and their origins in a benthic marine organism with one of the longest pelagic larval phases, the Caribbean spiny lobster (Panulirus argus). We genotyped newly settled postlarvae in the Florida Keys and adults of spiny lobster from the Florida Keys and throughout the Caribbean Sea. We identified strong larval connectivity between Dominican Republic, Belize, Nicaragua, the Florida Keys, and West-Florida. The larval dispersal modeling suggests that Florida's lobster population could receive recruits from within and from other areas outside its state and national maritime boundaries. The genetic analyses refine the oceanographic model indicating that the connectivity patterns described could also result from unknown parental populations sourcing adults and postlarvae in different spawning seasons to the Florida Keys. We discuss the importance of small temporal scales to identify patterns in larval export. Our findings are significant on two levels. From the larval dispersal perspective, genetic results and biophysical modeling identify patterns of gene flow enhancing persistence of local populations. From an economic and fishery perspective, P. argus is the most important commercial species in the Caribbean and our results inform how considering larval source and sink dynamics across international boundaries could improve management plans at local, national, and regional levels.

New quinone antibiotics of the granaticin type, isolated from Streptomyces lateritius. II. Structure determination.

A number of new granaticin type quinone antibiotics have been isolated from Streptomyces lateritus ATCC 19913. Spectroscopic evidence is presented which has led to the structure elucidation of three new antibiotics and the chemical relationship between members of the granaticin series has been studied.

Four further antibiotics related to olivanic acid produced by Streptomyces olivaceus: fermentation, isolation, characterisation and biosynthetic studies.

Four beta-lactam antibiotics with beta-lactamase inhibitory activity MM 22380, MM 22381, MM 22382 and MM 22383 containing the carbapenem nucleus have been isolated from a culture of Streptomyces olivaceus ATCC 31365. Fermentation conditions for their production and methods for their isolation are described. Evidence for a biosynthetic link between these compounds and the previously described olivanic acid derivatives MM 4550, MM 13902 and MM 17880 is presented.

Olivanic acids, a family of beta-lactam antibiotics with beta-lactamase inhibitory properties produced by Streptomyces species. II. Isolation and characterisation of the olivanic acids MM 4550, MM 13902 and MM 17880 from Streptomyces olivaceus.

The olivanic acids MM 4550, MM 13902 and MM 17880 are members of a new family of beta-lactam antibiotics. An isolation and purification process utilising ion-par extraction and ion-exchange chromatography is described and the metabolites are characterised by physico-chemical and biological properties.

MM 42842, a new member of the monobactam family produced by Pseudomonas cocovenenans. I. Identification of the producing organism.

A bacterial soil isolate designated 326-32B produces a new member of the monobactam series of antibiotics, MM 42842, and the bulgecins. Identification studies show isolate 326-32B to be a strain of Pseudomonas cocoveneans which is a species previously noted for the production of toxoflavin. A description of P. cocovenenans does not appear to have been previously published and the identify of strain 326-32B was established by means of a direct comparison with the deposited organism P. cocovenenans NCIB 9450. The properties of strain 326-32B, and P. cocovenenans NCIB 9450 were compared with those of the monobactam and bulgecin producing organisms Pseudomonas acidophila ATCC 31363 and Pseudomonas mesoacidophila ATCC 31433. The four organisms were found to share certain properties, including the ability to grow at pH 4.0.

MM 42842, a new member of the monobactam family produced by Pseudomonas cocovenenans. II. Production, isolation and properties of MM 42842.

A new member of the monobactam family of beta-lactam antibiotics, designated MM 42842, has been detected in a culture of Pseudomonas cocovenenans. The production, isolation and some properties of the antibiotic are described. Structural studies show MM 42842 to be closely related to the previously described antibiotic sulfazecin.

The biosynthetic implications of acetate and glutamate incorporation into (3R,5R)-carbapenam-3-carboxylic acid and (5R)-carbapen-2-em-3-carboxylic acid by Serratia sp.

Two new beta-lactams have been isolated from strains of Serratia and Erwinia sp. and identified as (3R,5R)- and (3S,5R)-carbapenam-3-carboxylic acid. These novel carbapenams lack antibacterial activity, are resistant to both beta-lactamases I and II from Bacillus cereus and are not detected by the lactamase induction assay. Radiolabelled and stable isotope experiments have established that both metabolites together with the antibiotic 5R-carbapenem-3-carboxylic acid are glutamate and acetate derived. A number of possible pathways for the biosynthesis of these compounds as well as their relationship to the more complex members of the carbapenem family of beta-lactam antibiotics are discussed.

MM 14201, a new epoxyquinone derivative with antibacterial activity produced by a species of Streptomyces.

A new antibiotic designated MM 14201 has been detected in a culture of Streptomyces sp. NCIB 11813. Methods for the production and purification of MM 14201 are described. Biological evaluation has shown it has broad spectrum antibacterial activity being most effective against Serratia and Pseudomonas sp. Structural studies are reported which have demonstrated MM 14201 is a new epoxyquinone derivative.

MM 47761 and MM 49721, glycopeptide antibiotics produced by a new strain of Amycolatopsis orientalis. Isolation, purification and structure determination.

Two glycopeptide antibiotics MM 47761 and MM 47921 have been isolated from Amycolatopsis orientalis NCIB 12608. Fermentation conditions for their production, and methods for their isolation are described. The metabolites have been characterised by physio-chemical and biological properties and the structure determined by a combination of chemical degradation, COSY and NOE NMR studies. Both metabolites showed good antibacterial activity against Gram-positive organisms.

MM 55266 and MM 55268, glycopeptide antibiotics produced by a new strain of Amycolatopsis. Isolation, purification and structure determination.

Two novel glycopeptide antibiotics MM 55266 and MM 55268 containing fatty acid acyl functions, and of molecular formula C86H89N8O35Cl5 and C87H91N8O35Cl5, respectively, have been isolated and identified from a complex produced by Amycolatopsis sp. NCIB 40089. Fermentation conditions for their production, and methods for their isolation are described. Structures have been deduced by use of COSY and NOE NMR techniques and supported by chemical degradation studies. Both glycopeptides possessed good antibacterial activity against Gram-positive organisms.

Comparative biological properties of some synthetic olivanic acid analogues.

A series of olivanic acid/thienamycin analogues have been prepared by total synthesis. Particular attention was given to the effect of the side-chain substituents on the chemical, beta-lactamase and metabolic stability of the final products. All of the compounds possessed a broad and high level of in vitro antibacterial activity against Gram-positive and Gram-negative organisms including beta-lactamase-producing strains. Two derivatives (8c) and (8j) were selected for further evaluation on the basis of in vitro activity, ease of synthesis and stability parameters. The improved metabolic stability of the selected analogues, relative to the naturally-occurring olivanic acid, MM 13902, could be demonstrated in terms of better activity, higher blood levels and improved urinary recovery in in vivo studies in mice.

Properties of MM 13902 and other carbapenem antibiotics in vitro and in vivo.

The carbapenem antibiotics, which include the olivanic acids and the thienamycins, have a broad-spectrum of antibacterial activity but only thienamycin itself shows appreciable activity against Pseudomonas aeruginosa. The zwitterionic nature of thienamycin was reproduced in the olivanic acid series by preparing the deacetyl derivatives of MM 17880 and MM 22380--compounds NA 26975 and NA 26978. The latter derivative showed antipseudomonas activity and had an antibacterial spectrum similar to thienamycin itself. In contrast the O-sulfated analogue, NA 26975, was no more active than the parent compound against P. aeruginosa. Both deacetyl compounds were more stable than the parent natural products to a mouse kidney enzyme preparation and gave higher urinary recoveries in the mouse. Pharmacokinetic studies with MM 13902 in various animal species showed that the compound was rapidly eliminated from the blood and gave only low urinary recoveries. Similar findings were observed also in human volunteers given MM 13902. The nephrotoxicity reported for thienamycin/MK 0787 in the rabbit was not seen with the olivanic acids MM 13902, MM 17880, MM 22382 and MM 22383 when tested under the same conditions.

Prasinons A and B: potent insecticides from Streptomyces prasinus.

Two metabolites which have high activity against sheep blowfly larvae (Lucilia sericata and L. cuprina) were found to be produced by Streptomyces prasinus NCIB 10719. These substances were isolated from culture filtrate by solvent extraction and chromatography and named prasinons A and B. Fermentation factors affecting the formation of these substances are described together with their physical, chemical, and biological properties.