Biotechnology
Clavulanic Acid and Clavams
Clavulanic Acid and Clavams Biosynthesis and Regulation
from Paloma Liras, Irene Santamarta and Rosario Pérez-Redondo writing in Streptomyces: Molecular Biology and Biotechnology:
The (3R,5R) clavulanic acid and (3S,5S) clavam molecules share a structure formed by a four member β-lactam and a five member oxaxolidine ring and have several initial common steps in their biosynthesis pathways. The precursors of the molecules are glyceraldehyde-3-phosphate and arginine, condensed by the carboxyethylarginine synthetase (CeaS). The next steps in the pathway occur by the subsequent action of the β-lactam synthase (Bls) forming the β-lactam ring, a proclavaminic acid guanidine hydrolase (PAH) and the clavaminate synthase (Csa2), which forms the two rings clavam structure of clavaminic acid. Modifications of this compound result in late step intermediates for clavulanic acid biosynthesis, N-glycylclavaminic acid or clavaldehyde, and in the clavams structures. In addition to the clavulanic acid gene cluster, two additional clusters containing paralogous genes for clavulanic acid biosynthesis and clavam biosynthesis have been located in S. clavuligerus. Biochemical characterization of the clavam non producer mutants will clarify the biosynthetic pathway of these compounds.
Further reading: Streptomyces: Molecular Biology and Biotechnology
from Paloma Liras, Irene Santamarta and Rosario Pérez-Redondo writing in Streptomyces: Molecular Biology and Biotechnology:
The (3R,5R) clavulanic acid and (3S,5S) clavam molecules share a structure formed by a four member β-lactam and a five member oxaxolidine ring and have several initial common steps in their biosynthesis pathways. The precursors of the molecules are glyceraldehyde-3-phosphate and arginine, condensed by the carboxyethylarginine synthetase (CeaS). The next steps in the pathway occur by the subsequent action of the β-lactam synthase (Bls) forming the β-lactam ring, a proclavaminic acid guanidine hydrolase (PAH) and the clavaminate synthase (Csa2), which forms the two rings clavam structure of clavaminic acid. Modifications of this compound result in late step intermediates for clavulanic acid biosynthesis, N-glycylclavaminic acid or clavaldehyde, and in the clavams structures. In addition to the clavulanic acid gene cluster, two additional clusters containing paralogous genes for clavulanic acid biosynthesis and clavam biosynthesis have been located in S. clavuligerus. Biochemical characterization of the clavam non producer mutants will clarify the biosynthetic pathway of these compounds.
Further reading: Streptomyces: Molecular Biology and Biotechnology
Bioactive Natural Products in Actinomycetes
Gene Clusters for Bioactive Natural Products in Actinomycetes and their Use in Combinatorial Biosynthesis
from Carlos Olano, Carmen Méndez and José A. Salas writing in Streptomyces: Molecular Biology and Biotechnology:
During the last twenty five years the isolation and characterization of gene clusters involved in the biosynthesis of actinomycete secondary metabolites has permitted the elucidation of the biochemical steps involved in the production of different structural classes of bioactive compounds. The characterization of these clusters has represented a great source of genes for the generation of novel "unnatural natural" compounds by using combinatorial biosynthesis. The development of more effective methods for DNA sequencing, the improvement of targeted inactivation and heterologous host expression systems has strengthened the effectiveness of combinatorial biosynthesis. For these reasons combinatorial DNA technology has become during the last decade one of the most important approaches for generating chemical structural diversity and for increasing the number of potential useful compounds.
Further reading: Streptomyces: Molecular Biology and Biotechnology
from Carlos Olano, Carmen Méndez and José A. Salas writing in Streptomyces: Molecular Biology and Biotechnology:
During the last twenty five years the isolation and characterization of gene clusters involved in the biosynthesis of actinomycete secondary metabolites has permitted the elucidation of the biochemical steps involved in the production of different structural classes of bioactive compounds. The characterization of these clusters has represented a great source of genes for the generation of novel "unnatural natural" compounds by using combinatorial biosynthesis. The development of more effective methods for DNA sequencing, the improvement of targeted inactivation and heterologous host expression systems has strengthened the effectiveness of combinatorial biosynthesis. For these reasons combinatorial DNA technology has become during the last decade one of the most important approaches for generating chemical structural diversity and for increasing the number of potential useful compounds.
Further reading: Streptomyces: Molecular Biology and Biotechnology
Streptomyces book
Paul Dyson (Institute of Life Sciences, School of Medicine, Swansea, UK) presents a new book on Streptomyces: Molecular Biology and Biotechnology
Streptomycetes are Gram-positive, high GC-content, sporulating bacteria found predominantly in soil. Streptomycetes are characterised by a complex secondary metabolism producing antibiotic compounds and other metabolites with medicinal properties. In recent years genomic studies, genomic mining and biotechnological approaches have been employed in the search for new antibiotics and other drugs.
With contributions from some of the leading scientists in the field, this volume documents recent research and development in streptomycetes genomics, physiology and metabolism. With a focus on biotechnology and genomics, the book provides an excellent source of up-to-date information. Topics include: genome architecture, conjugative genetic elements, differentiation, protein secretion, central carbon metabolic pathways, regulation of nitrogen assimilation, phosphate control of metabolism, gamma-butyrolactones and their role in antibiotic regulation, clavulanic acid and clavams, genome-guided exploration, gene clusters for bioactive natural products, genomics of cytochromes p450.
Streptomycetes are Gram-positive, high GC-content, sporulating bacteria found predominantly in soil. Streptomycetes are characterised by a complex secondary metabolism producing antibiotic compounds and other metabolites with medicinal properties. In recent years genomic studies, genomic mining and biotechnological approaches have been employed in the search for new antibiotics and other drugs.
With contributions from some of the leading scientists in the field, this volume documents recent research and development in streptomycetes genomics, physiology and metabolism. With a focus on biotechnology and genomics, the book provides an excellent source of up-to-date information. Topics include: genome architecture, conjugative genetic elements, differentiation, protein secretion, central carbon metabolic pathways, regulation of nitrogen assimilation, phosphate control of metabolism, gamma-butyrolactones and their role in antibiotic regulation, clavulanic acid and clavams, genome-guided exploration, gene clusters for bioactive natural products, genomics of cytochromes p450.
 | Edited by: Paul Dyson ISBN: 978-1-904455-77-6 Publisher: Caister Academic Press Publication Date: January 2011 Cover: hardback |
Essential reading for research scientists, biotechnologists, graduate students and other professionals involved in streptomycetes research, antibiotic and antimicrobial development, drug discovery, soil microbiology and related fields. A recommended text for all microbiology laboratories.