Antibiotics, biosynthesis and

Ristow H, Russo J, Stochaj E, Paulus H (1982) In Kleinkauf H, von Dohren H (eds) Peptide antibiotics - biosynthesis and functions. Walter de Gruyter, Berlin, p 381... 

D. J. Hook, R.P. Elander, R.B. Morin, Recent developments with cell free extracts on the enzymic biosynthesis of penicillins and cephalosporins in Peptide-antibiotics . Biosynthesis and Function, H. Kleinkauf, H. von Dohren eds. de Gruyter, Berlin 1982, pp 84-100... 

McCann, Regulation of antibiotic biosynthesis and differentiation in streptomycetes, Microbiology 1976, 543. ———... 

Seno ET, Baltz RH. Stnictural organizaiion and regulation of antibiotic biosynthesis and resistance genes in actinomycetes. Shapiro S, ed. Regulation of Secondary Metabolism in Actinomycetes. Boca Raton, Florida CRC Press, 1989 1-48. 

Classical genetic mapping and molecular cloning studies have revealed that antibiotic biosynthesis and resistance genes are invariably clustered on the chromosomes of Strepio-myces and other actinomycetes (92.93). In keeping with this general rule, the penicillin/cephalosporin biosynthetic genes from all bacterial >ecies studied to date have... 

P-lactam antibiotics, exert thek antibacterial effect by interfering with the synthesis of the bacterial cell wall. These antibiotics tend to be "kreversible" inhibitors of cell wall biosynthesis and they are usually bactericidal at concentrations close to thek bacteriostatic levels. Cephalospotins are widely used for treating bacterial infections. They are highly effective antibiotics and have low toxicity. 

The Shikimate pathway is responsible for biosynthesis of aromatic amino acids in bacteria, fungi and plants [28], and the absence of this pathway in mammals makes it an interesting target for designing novel antibiotics, fungicides and herbicides. After the production of chorismate the pathway branches and, via specific internal pathways, the chorismate intermediate is converted to the three aromatic amino acids, in addition to a number of other aromatic compounds [29], The enzyme chorismate mutase (CM) is a key enzyme responsible for the Claisen rearrangement of chorismate to prephenate (Scheme 1-1), the first step in the branch that ultimately leads to production of tyrosine and phenylalanine. 

Walsh, C.T. (2002) Combinatorial biosynthesis of antibiotics challenges and opportunities. Chembiochem A European Journal of Chemical Biology, 3, 125. 

Pacholec, M., Tao, J. and Walsh, C.T. (2005) CouO and NovO C-methyltransferases for tailoring the aminocoumarin scaffold in coumermycin and novobiocin antibiotic biosynthesis. Biochemistry, 44, 14969-14976. 

Ovchinnikov, Yu. A., Ivanov, V. T., Shkrob, A. M. In Molecular mechanisms of antibiotic action on protein biosynthesis and membranes (E. Munoz, F. Garcia-Femandez and D. Vasquez, eds.), p. 459. Amsterdam Elsevier 1972. 

This is a complex molecule, made up of an adenine nucleotide (ADP-3 -phosphate), pantothenic acid (vitamin B5), and cysteamine (2-mercaptoethylamine), but for mechanism purposes can be thought of as a simple thiol, HSCoA. Pre-eminent amongst the biochemical thioesters is the thioester of acetic acid, acetyl-coenzyme A (acetyl-CoA). This compound plays a key role in the biosynthesis and metabolism of fatty acids (see Sections 15.4 and 15.5), as well as being a building block for the biosynthesis of a wide range of natural products, such as phenols and macrolide antibiotics (see Box 10.4). 

The General myo-lnositol and scyllo-Inosamine Pathway. Two distinct cyclitol pathways, which we earlier called Ca (started by myo-inositolphos-phate synthase) and Cb (started by T-deoxy-i cy/to-inosose synthase), are used in the initiation of AGA pathways. Here we will describe the Ca route and the Cb pathway in the paragraph on NEOs (see Section 2.2.2.1.3). The cyclitol pathway in the biosynthetic pathways for STRs, but also for other AGAs such as SPCs, KAS, and FORs and also the mixed type antibiotic HYG-A (see Section 2.2.4.3.1), starts with the formation of myo-inositol in a two-step pathway (Ca) that is not encoded in the itrAtt-clusters. The first step in streptidine biosynthesis (and any other myo-inositol utilising pathway) is the formation of a myo-inositol monophosphate (D-myo-inositol-3-phosphate or L-myo-inositol-1-phosphate) via L-myo-inositol-1-phosphate synthase, which in actinomycetes... 

Piepersberg, W. Streptomycin and related aminoglycosides. In Biochemistry and Genetics of Antibiotic Biosynthesis Vining, L. Stuttard, C., Eds. Boston Butterworth-Heinemann, 1995 pp. 531-570. 

Okuda, T. Ito, Y. Biosynthesis and mutasynthesis of aminoglycoside antibiotics. In Aminoglycoside Antibiotics Umezawa, H. Hooper IR., Eds. Berlin Springer-Verlag, 1982 pp. 111-203. 

Piepersberg W, Streptomycin and related aminoglycosides In Vining LC, Stut-tard C (eds.), Biochemistry and Genetics of Antibiotic Biosynthesis Butterworths-Heinemann, Boston, MA, pp. 531—570, 1999. 

Grell, E., Funck, Th., Eggers, F. Symposium on Molecular Mechanisms of Antibiotic Action on Protein Biosynthesis and Membranes, University of Granada, Spain, June 1—4 (1971). 

This type of alkylation also occurs in nature. For example, S-adenosylmethionine (SAM), an important biological methylation reagent, is involved in the biosynthesis of the antibiotic indolmycin and is responsible for the enantioselective C-methylation of an a-oxocarboxylic acid arising from tryptophan3. 

It is somewhat surprising to find that there have been only three published reviews on tetramic acids. The first reports on the advances in tetramic acid chemistry up to 1993 [1], another describes the synthesis of tetramic acid antibiotics [3], and a third, dealing with the structure, isolation and synthesis of naturally occurring tetramic acids, was published in 1995 [4]. The present review is an attempt to cover the field of tetramic acid metabolites with particular emphasis on the structure, biosynthesis and biological activity of these compounds. 

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