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New space-filling atomic-molecular models
TIBTECH
Screening microorganisms
A rapid assay has been designed that (1) assesses the polychlorinated biphenyl (PCB)-degradative competence and congener specificity of aerobic microorganisms, (2) identifies strains capable of degrading highly chlorinated biphenyls, and (3) distinguishes~among those that degrade PCBs by alternative pathways. Prior attempts to assay PCB-degradative competence by measuring disappearance of Aroclors (commercial PCB mixtures) have frequently produced false-positive findings because of volatilization, adsorption, or absorption losses. Furthermore, these assays have generally left the
for PCB degradation
chemical nature of the competence obscure because of incomplete gas chromatographic resolution and uncertain identification of Aroclor peaks. These problems were avoided by using defined mixtures of PCB congeners and by adopting incubation and extraction methods that prevent physical loss of PCBs. Assay mixtures include PCB congeners ranging from dichloro- to hexachlorobiphenyls and representing various structural classes, e.g. congeners chlorinated on a single ring (2,3-dichlorobiphenyl), blocked at 2,3-sites (2,5,2'5'tetrachlorobiphenyl), blocked at 3,4 sites
New space-filling atomic-molecular
The best space-filling atomic models presently available were elaborated 20-25 years ago largely for modelling small molecules and it can be difficult to reconcile them with present-day data on valence angles and interatomic distances or to use them for exact modelling of macromolecular conformation. A new type of space-filling atomicmolecular model has been designed based on recent research, in crystallography, conformation calculation and Xray analysis. The inexpensive space-
models
filling models have been constructed from coloured plastic spheres with flat faces. Connectors model interatomic bonds, and angles between them stand for valence angles. The radius of the sphere corresponds to the van der Waals' radius of the atom, and the distance from the centre to the plane of intersection of the spheres represents the covalent radius of the atom. The atoms are colour-coded: hydrogen, white; carbon, black; oxygen, red; nitrogen, blue; phosphor, orange; sulphur, yellow; etc. (Figs 1-3). Other
- - Fig. 1
Model of lecithin.
- JUNE
1 986
(4,4'-dichlorobiphenyl), and lacking adjacent unchlorinated sites (2,4,5,2',4',5'hexachlorobiphenyl). The PCB-degradarive ability of microorganisms is assessed by packed-column gas chromatographic analysis of these defined congener mixtures following 24 h incubation with resting cells. When tested with 25 environmental isolates, this assay (1) revealed a broad range of PCB-degradative competence, (2) highlighted differences in congener specificity and in the extent of degradation of individual congeners, (3) predicted degradative competence on commercial PCBs, and (4) identified strains with superior PCBdegradative ability. Bedard, D. L., Unterman, R., Bopp, L. H., Brennan, M.J., Haberl, M.L. and Johnson, C. (1986) App]. Env. Microbiol. 51,761-768
special units have been added, for example phosphorus and oxygen units for modelling sugar-phosphate chains and a carbon unit for constructing fivemembered aplanar cyclic compounds, which makes it possible to model the Aand B-classes of nucleic acids with good accuracy. The new type of models allows measurement of atomic coordinates and dihedral conformation angles and building of complex three-dimensional structures directly from electron density maps. A nomenclature of units has been worked out, which has made it possible to draw up clear schemes for assembling nucleotides and amino acids. The new kits permit rapid modelling of the structure
--Fig. 2
Model o f guanyl-ribobisphosphate in 2'-endo and 3'endo conformation
© 1986,ElsevierSciencePublishersB.V.,Amsterdam 0166-9430/86/$02.00
For technical reasons we are unable to reproduce this figure in colour. See the June edition of Trends in Biotechnology for full colour illustration.
T I B T E C H - J U N E 1986
and conformational changes not only of micromolecules but also large biomolecules. The elaborators of the new precision space-filling atomicmolecular models believe that they are a cheap reliable aid to research and teaching. For further information contact Cambridge BioScience, 42 Devonshire Road, Cambridge CB1 2BL, UK (telephone, 0223 316855; telex, 81304 CBIOSC G); Licensnauka, V/O Licensintorg, Minsk Street 11,121 108 Moscow, USSR (telephone, 14505-74; telex, 411 246 or 411 415); Department of Experimental Design, Tartu State University, 18 13fikooli Street, Tartu 202400, Estonian SSR, USSR (telephone, 32361).
--Fig. 3
Mikelsaar, R-H. N., Bruskov, V. I., Poltev, V.I. (1985) New Precision Space-filling Atomic-molecular Models, Pushchino Contributed by Raik Mikelsaar, Institute of General and Molecular Pathology, Tartu State University, 202400 Burdenko Street 34, Tartu, Estonian SSR, USSR.
Model of B-DNA.
A sensor for measuring urea in blood
low resistance, the measuring circuit for the sensor can be greatly simplified.
Several sensors for urea have been designed which use the enzyme urease to produce a pH change by breaking down urea. If the enzyme is coupled to a pH electrode, the concentration of urea in the sample can be determined. If a conventional glass pH electrode is used, the sensor size and configuration can be limited by the pH electrode. However, by using antimony electrodes, this limitation can be overcome. In addition, because the antimony electrodes exhibit a
Kulys, J. J., Gurevi~iene, V.V., Laurinavi(~ius, U. A. and Jonugka, A. V. (1986) Biosensors 2, 3 4 4 4
A Great Epic of
Biotechnology
PENICILLIN: MEETING THE CHALLENGE
by Gladys L. Hobby, Yale University Press, 1985. £30.00 (xxii + 319pages) ISBN 0 300 03225 0 F l e m i n g ' s role in the discovery and d e v e l o p m e n t of p e n i c i l l i n has undergone a radical reassessment that has led to a better appreciation of the w o r k of Florey, Chain and the Oxford Group. This reassessment stems from Ronald Hare's meticulous research and has resulted in the excellent biographies of Florey by
Removing endotoxin by microfiltration
processes. Filtration methods such as reverse osmosis and ultrafiltration have been unsuitable because of low water flow rates. However, using a microporous filter made of polyethylene hollow fiber, a water purification device which removes endotoxin was developed. The device combined adsorption and filtration principles and could be regenerated to a certain extent by w a s h i ~ with a solution of alkaline ethanol.
Reliable methods are still required for removing endotoxin, a pyrogen, from water used in many manufacturing
Sawada, Y., Fujii, R., Zgami, I., Kawai, A., Kamiki, T. and Nina, M. (1986) Appl. Env. Microbiol. 51,813-820
MacFarlane and Williams, and those of F l e m i n g by MacFarlane and of Chain by Clark. This book by Gladys Hobby is the latest contribution to the histories of p e n i c i l l i n and deals w i t h the c o m m e r c i a l d e v e l o p m e n t and exploitation of penicillin. It is surprising that this part of the story has been neglected, for it is clearly one of the great epics of biotechnology. In 1941 Florey asked the A m e r i c a n s to produce some 5 m i l l i o n units of penicillin; in 1943 21 billion units were produced! Hobby begins w i t h her version of the discovery of p e n i c i l l i n and the reasons for Fleming's failure to d e v e l o p it. I do not find her's a
satisfactory account and I recomm e n d instead MacFarlane's books and Ronald Hare's articles (Medical History 26, 1-24, 1982). Hobby does, however, do justice to the pioneering but u n k n o w n w o r k of Lewis Holt and to the critical part played by N o r m a n Heatley in p r o d u c i n g sufficient penicillin for the Oxford team to use clinically. Hobby makes clear h o w this depended on Heatley's ingenuity, hard work and ability to improvise. Hobby's account comes into its o w n w h e n she carries the story b e y o n d the visit of Florey and Heatley to the U S A in 1941. She was intimately i n v o l v e d in this phase of the p e n i c i l l i n story and describes the transition from small scale clinical trials and p r o d u c t i o n to massive p r o d u c t i o n and correspondingly extensive trials. Hobby discusses commercial p r o d u c t i o n in the UK as well
1986,Elsevier Science Publishers B.V., Amsterdam 0165- 6147/86/$02.00 For t e c h n i c a l r e a s o n s w e are u n a b l e to r e p r o d u c e t h i s f i g u r e i n c o l o u r . See the J u n e e d i t i o n of Trends in Biotechnology for full c o l o u r
illustration.
Screening microorganisms
A rapid assay has been designed that (1) assesses the polychlorinated biphenyl (PCB)-degradative competence and congener specificity of aerobic microorganisms, (2) identifies strains capable of degrading highly chlorinated biphenyls, and (3) distinguishes~among those that degrade PCBs by alternative pathways. Prior attempts to assay PCB-degradative competence by measuring disappearance of Aroclors (commercial PCB mixtures) have frequently produced false-positive findings because of volatilization, adsorption, or absorption losses. Furthermore, these assays have generally left the
for PCB degradation
chemical nature of the competence obscure because of incomplete gas chromatographic resolution and uncertain identification of Aroclor peaks. These problems were avoided by using defined mixtures of PCB congeners and by adopting incubation and extraction methods that prevent physical loss of PCBs. Assay mixtures include PCB congeners ranging from dichloro- to hexachlorobiphenyls and representing various structural classes, e.g. congeners chlorinated on a single ring (2,3-dichlorobiphenyl), blocked at 2,3-sites (2,5,2'5'tetrachlorobiphenyl), blocked at 3,4 sites
New space-filling atomic-molecular
The best space-filling atomic models presently available were elaborated 20-25 years ago largely for modelling small molecules and it can be difficult to reconcile them with present-day data on valence angles and interatomic distances or to use them for exact modelling of macromolecular conformation. A new type of space-filling atomicmolecular model has been designed based on recent research, in crystallography, conformation calculation and Xray analysis. The inexpensive space-
models
filling models have been constructed from coloured plastic spheres with flat faces. Connectors model interatomic bonds, and angles between them stand for valence angles. The radius of the sphere corresponds to the van der Waals' radius of the atom, and the distance from the centre to the plane of intersection of the spheres represents the covalent radius of the atom. The atoms are colour-coded: hydrogen, white; carbon, black; oxygen, red; nitrogen, blue; phosphor, orange; sulphur, yellow; etc. (Figs 1-3). Other
- - Fig. 1
Model of lecithin.
- JUNE
1 986
(4,4'-dichlorobiphenyl), and lacking adjacent unchlorinated sites (2,4,5,2',4',5'hexachlorobiphenyl). The PCB-degradarive ability of microorganisms is assessed by packed-column gas chromatographic analysis of these defined congener mixtures following 24 h incubation with resting cells. When tested with 25 environmental isolates, this assay (1) revealed a broad range of PCB-degradative competence, (2) highlighted differences in congener specificity and in the extent of degradation of individual congeners, (3) predicted degradative competence on commercial PCBs, and (4) identified strains with superior PCBdegradative ability. Bedard, D. L., Unterman, R., Bopp, L. H., Brennan, M.J., Haberl, M.L. and Johnson, C. (1986) App]. Env. Microbiol. 51,761-768
special units have been added, for example phosphorus and oxygen units for modelling sugar-phosphate chains and a carbon unit for constructing fivemembered aplanar cyclic compounds, which makes it possible to model the Aand B-classes of nucleic acids with good accuracy. The new type of models allows measurement of atomic coordinates and dihedral conformation angles and building of complex three-dimensional structures directly from electron density maps. A nomenclature of units has been worked out, which has made it possible to draw up clear schemes for assembling nucleotides and amino acids. The new kits permit rapid modelling of the structure
--Fig. 2
Model o f guanyl-ribobisphosphate in 2'-endo and 3'endo conformation
© 1986,ElsevierSciencePublishersB.V.,Amsterdam 0166-9430/86/$02.00
For technical reasons we are unable to reproduce this figure in colour. See the June edition of Trends in Biotechnology for full colour illustration.
T I B T E C H - J U N E 1986
and conformational changes not only of micromolecules but also large biomolecules. The elaborators of the new precision space-filling atomicmolecular models believe that they are a cheap reliable aid to research and teaching. For further information contact Cambridge BioScience, 42 Devonshire Road, Cambridge CB1 2BL, UK (telephone, 0223 316855; telex, 81304 CBIOSC G); Licensnauka, V/O Licensintorg, Minsk Street 11,121 108 Moscow, USSR (telephone, 14505-74; telex, 411 246 or 411 415); Department of Experimental Design, Tartu State University, 18 13fikooli Street, Tartu 202400, Estonian SSR, USSR (telephone, 32361).
--Fig. 3
Mikelsaar, R-H. N., Bruskov, V. I., Poltev, V.I. (1985) New Precision Space-filling Atomic-molecular Models, Pushchino Contributed by Raik Mikelsaar, Institute of General and Molecular Pathology, Tartu State University, 202400 Burdenko Street 34, Tartu, Estonian SSR, USSR.
Model of B-DNA.
A sensor for measuring urea in blood
low resistance, the measuring circuit for the sensor can be greatly simplified.
Several sensors for urea have been designed which use the enzyme urease to produce a pH change by breaking down urea. If the enzyme is coupled to a pH electrode, the concentration of urea in the sample can be determined. If a conventional glass pH electrode is used, the sensor size and configuration can be limited by the pH electrode. However, by using antimony electrodes, this limitation can be overcome. In addition, because the antimony electrodes exhibit a
Kulys, J. J., Gurevi~iene, V.V., Laurinavi(~ius, U. A. and Jonugka, A. V. (1986) Biosensors 2, 3 4 4 4
A Great Epic of
Biotechnology
PENICILLIN: MEETING THE CHALLENGE
by Gladys L. Hobby, Yale University Press, 1985. £30.00 (xxii + 319pages) ISBN 0 300 03225 0 F l e m i n g ' s role in the discovery and d e v e l o p m e n t of p e n i c i l l i n has undergone a radical reassessment that has led to a better appreciation of the w o r k of Florey, Chain and the Oxford Group. This reassessment stems from Ronald Hare's meticulous research and has resulted in the excellent biographies of Florey by
Removing endotoxin by microfiltration
processes. Filtration methods such as reverse osmosis and ultrafiltration have been unsuitable because of low water flow rates. However, using a microporous filter made of polyethylene hollow fiber, a water purification device which removes endotoxin was developed. The device combined adsorption and filtration principles and could be regenerated to a certain extent by w a s h i ~ with a solution of alkaline ethanol.
Reliable methods are still required for removing endotoxin, a pyrogen, from water used in many manufacturing
Sawada, Y., Fujii, R., Zgami, I., Kawai, A., Kamiki, T. and Nina, M. (1986) Appl. Env. Microbiol. 51,813-820
MacFarlane and Williams, and those of F l e m i n g by MacFarlane and of Chain by Clark. This book by Gladys Hobby is the latest contribution to the histories of p e n i c i l l i n and deals w i t h the c o m m e r c i a l d e v e l o p m e n t and exploitation of penicillin. It is surprising that this part of the story has been neglected, for it is clearly one of the great epics of biotechnology. In 1941 Florey asked the A m e r i c a n s to produce some 5 m i l l i o n units of penicillin; in 1943 21 billion units were produced! Hobby begins w i t h her version of the discovery of p e n i c i l l i n and the reasons for Fleming's failure to d e v e l o p it. I do not find her's a
satisfactory account and I recomm e n d instead MacFarlane's books and Ronald Hare's articles (Medical History 26, 1-24, 1982). Hobby does, however, do justice to the pioneering but u n k n o w n w o r k of Lewis Holt and to the critical part played by N o r m a n Heatley in p r o d u c i n g sufficient penicillin for the Oxford team to use clinically. Hobby makes clear h o w this depended on Heatley's ingenuity, hard work and ability to improvise. Hobby's account comes into its o w n w h e n she carries the story b e y o n d the visit of Florey and Heatley to the U S A in 1941. She was intimately i n v o l v e d in this phase of the p e n i c i l l i n story and describes the transition from small scale clinical trials and p r o d u c t i o n to massive p r o d u c t i o n and correspondingly extensive trials. Hobby discusses commercial p r o d u c t i o n in the UK as well
1986,Elsevier Science Publishers B.V., Amsterdam 0165- 6147/86/$02.00 For t e c h n i c a l r e a s o n s w e are u n a b l e to r e p r o d u c e t h i s f i g u r e i n c o l o u r . See the J u n e e d i t i o n of Trends in Biotechnology for full c o l o u r
illustration.