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A novel [beta]-N-acetylglucosaminidase (GlcNAcase) inhibitor named TMG-chitotriomycin is isolated from the culture filtrate of Streptomyces anulates NBRC 13369. The results have shown that the [(GlcNAc).sub.3] unit positioned at the reducing end of TMG-chitotriomycin is necessary for its enzyme inhibitory activity.

The biosynthesis of the antibiotics acivicin and 4-hydroxyacivicin was studied in Streptomyces sviceus. It was shown that ornithine, rather than glutamic acid or glutamine, is the primary precursor, and that N(super delta)-hydroxyornithine, rather than erythro- or threo-beta-hydroxyornithine, is the first intermediate in the pathway. The results reveal that a linear pathway from ornithine via N(super delta)-hydroxyornithine leads to acivicin, which is then hydroxylated at C-4 to yield 4-hydroxyacivicin.

The stereochemistry of C-3 deoxygenation leading to formation of the metabolite pentopyranine C from (3-2H)-D-glucose by Streptomyces griseochromogenes was reported. Addition of (3-2H)-D-glucose to S. griseochromogenes fermentation containing arginine hydroxamate and cytosine led to accumulation of cytosylglucuronic acid and pentopyranine C. The relationship of this C-3 deoxygenation to blasticidin S biosynthesis and to cell-wall lipopolysaccharide biosynthesis in Gram-negative bacteria is discussed.

A comprehensive genetic, metabolomic and biochemical study on the catalytic properties of Streptomyces coelicolor cytochrome P450 (P450) 154A1, which has a unique heme orientation in its crystal structure, is described. The biotransformation of dipentaenone by P450 154A1 is an unexpected intramolecular cyclization to a Paterno-Buchi-like product, without oxidation/reduction.

The halogenase gene prnA from pyrrolnitrin biosynthesis was introduced into Streptomyces coeruleorubidus to perform an efficient in situ chlorination of the uridyl peptide antibotic pacidamycin. The installed chlorine provided a selectably functionalizable handle enabling synthetic modification of the natural product using mild cross-coupling conditions in crude aqueous extracts of the culture broth.

Mutasynthesis, biotransformation and combinatorial biosynthesis are used for generating a defined library of aureothin analogues. The studies have shown that various new aureothin derivatives are cytotoxic than aureothin but have improved antiproliferative activities and that the THF ring is important for the selective activity of aureothin analogous against certain pathogenic fungi.

Cloning, sequencing, heterologous expression, and mechanistic analysis of A-74528 biosynthesis, natural product of Streptomyces sp. which inhibits a key regulatory enzyme 2',5'-oligoadenylate phosphodiesterase (2'-PDE) of the interferon pathway is demonstrated. The gene A-74528 which is found to possess a type II polyketide synthase (PKS) at its core could have significant implications for the evolution of antibiotics with different biological activities from the same gene cluster.

The synthesis and characterization of new analogues resulting from inactivation of two tautomycetin (TTN) genes, ttnD and ttnF, in Streptomyces griseochromogenes are described. The results provide better insight into the transformations responsible for converting the post-polyketide synthase product into the exciting anticancer and immunosuppressive chemotherapeutic candidate TTN and significance of functional groups installed by TtnDF.

DesII from Streptomyces venezuelae is shown to consume SAM (S-adenosyl-L-methionine) versus TDP-sugar with various stoichiometries in the deamination and dehydrogenation reaction by using [Na.sub.2][S.sub.2][O.sub.4] as the reactant. The studies have not provided any evidence of an uncoupled or abortive process in the deamination reaction, as shown by the observation that dehydrogenation can take place in the absence of an external source of reductant whereas deamination cannot.

Calcium-dependent phosphatidylinositol-specific phospholipase C from Streptomyces antibioticus (saPLC1) has catalyzed hydrolysis of phosphatidylinositol (PI) into inositol 1-phosphate by a mechanism involving formation of inositol 1,6-cyclic phosphate (1,6-IcP) as an intermediate. The rates and products of cleavage of phosphorothioate and phosphorodithioate analogues of phosphatidylinositol (PI) in which sulfur is introduced into the phosphate moiety at a nonbridging position, a bridging position, or both are examined.

Several studies are conducted to explain the properties and differentiation of the numerous carbapenems, a clinically significant antibiotic family. The natural structural diversity observed in these antibiotics is shown to be highly dependent on the non-heme iron oxygenases.

The intramolecular electron transfer (ET) between the type 1 and the trinuclear copper center in small laccase (SLAC), which is a crucial step in the catalytic cycle of the multicopper oxidases, leading to dioxygen reduction to water, is examined. The ET step has depended on the reduction state of the enzyme, which has reflected site-site interactions that are not observed in other multicopper oxidases.

The article presents the identification, characterization and the biochemical analysis of the biosynthetic pathway of SF2575, an anticancer tetracycline polyketide. The functional reconstitution of several other enzymes is also discussed.

The secondary metabolites platensimycin and platencin, isolated from the bacterial strain Streptomyces platensis, have represented a novel class of natural products displaying potent antimicrobial activity. The syntheses of platecin have shown the power of the cobalt-catalyzed asymmetric Diels-Alder reaction and the one-pot reductive rearrangement of [3.2.1] bicyclic ketones to [2.2.2] bicyclic olefins.

Total synthesis of Ushikulide A isolated from a culture broth of Streptomyces sp. IUK-102 was performed to determine the full stereostructure of (-)-ushikulide A which exhibited potent immunosuppressant activity. The studies demonstrated the stereochemical assignment of (-)-ushikulide A and the extended scope of the total synthesis.

The first total synthesis, absolute configuration, and the biological evaluation of enantiomers of bisanthraquinone antibiotic BE-43472B isolated from a streptomycete strain and vancomycin-resistant Enterococcus faecalis (VRE) are described. The unnatural enantiomer [(-)-1] of antibiotic BE-43472B exhibited antibacterial properties comparable to those of the natural enantiomer [(+)-1].

Calcium-dependent phosphatidylinositol-specific phospholipase C from Streptomyces antibioticus (saPLC1) has catalyzed the cleavage of phosphatidylinositol (PI) by an unusual mechanism involving a 1,6-cyclization with formation of inositol trans-1,6-cyclic phosphate (1,6-IcP), rather than inositol cis-1,2-cyclic phosphate (1,2-IcP). This conclusion is based on the comparison of the released phosphate intermediate by the H16A mutant of saPLC1 with a genuine 1,6-IcP synthesized by a chemoenzymatic approach.

A two-step, cytochrome P450-catalyzed oxidation of epi-isozizaene synthase from Streptomyces coelicolor to yield antibiotic albaflavenone as final product is reported. A site-directed mutagenesis of active site residues in two universally conserved [Mg.sup.2+]-binding domains and the identification of six minor sesquiterpene products produced by the wild-type and mutant proteins provide insight into the mechanism and the role of the enzyme epi-isozizaene synthase.

The enzymes involved in spiroketal construction is identified by generating 14 gene-deletion variants of the griseorhodin A biosynthetic gene cluster isolated from the tunicate-associated bacterium Streptomyces sp. JP95. The absolute configuration of griseorhodin A is determined and the isolation of advanced intermediate lenticulone has shown that the spiroketal is formed by cleavage of four carbon-carbon bonds in a pentangular polyketide precursor.

The article discusses a new approach for the asymmetric total synthesis of (-)-quniocarcin from 3-hydroxybenzaldehyde. The method is shown to be highly easy, convergent and modular and hence can be easily used for the multigram synthesis.

The identification of the latest key intermediate in the biosynthesis of sesquiterpene, octalin and a side product of geosmin biosynthesis, octalin, are examined. The occurrence of (8S,9S,10S)-8,10-dimethyl-1-octalin (6,10-dimethylbicyclo[4.4.0]dec-2-ene) both under natural conditions and in enzyme preparations have indicated its key role in the biosynthesis of (-)-geosmin.

The preparation and structural studies of (+)-okilactomycin, a novel polyketide antitumor antibiotic isolated from a bioactive filtrate of Streptomyces griseoflavus is reported.

The article discusses the mechanisms involved in the identification and evolution of the fluorination enzyme from Streptomyces cattleya. The enzyme is found to be widely used for catalyzing the C-F bond formation reactions.

The function of remG and remH was investigated by performing gene inactivation, complementation and reconstruction of the biosynthetic pathway. The results show that only one of the two methyltransferases encoded in the rem gene cluster is needed for the introduction of two geminal methyl groups of resistomycin.

The biosynthesis of C-1027, an enediyne antitumor antibiotic by the regiospecific chlorination of (S)-[beta]-S-carrier protein catalyzed by SgcC3 is described.

The fredericamycin (FDM) A, is a pentadecaketide that features two groups of peri hydroxyl tricyclic aromatic moieties associated via a distinct chiral spiro carbon center, which shows effective cytotoxicity and is fully analyzed as an anticancer drug. The fdm gene cluster was localized to 33-kb DNA segment of Steptomyces griseus ATCC 49344, and its involvement in FDM A biosynthesis was proven by gene inactivation, complementation, and heterogonous expression experiments.