Biosynthesis of Diazepinomicin/ECO-4601, a Micromonospora Secondary Metabolite with a Novel Ring System

Peever

et al. 2010

Appl Environ Microbiol

233

231

Phenazines are versatile secondary metabolites of bacterial origin that function in biological control of plant pathogens and contribute to the ecological fitness and pathogenicity of the producing strains. In this study, we employed a collection of 94 strains having various geographic, environmental, and clinical origins to study the distribution and evolution of phenazine genes in members of the genera Pseudomonas, Burkholderia, Pectobacterium, Brevibacterium, and Streptomyces. Our results confirmed the diversity of phenazine producers and revealed that most of them appear to be soil-dwelling and/or plant-associated species. Genome analyses and comparisons of phylogenies inferred from sequences of the key phenazine biosynthesis (phzF) and housekeeping (rrs, recA, rpoB, atpD, and gyrB) genes revealed that the evolution and dispersal of phenazine genes are driven by mechanisms ranging from conservation in Pseudomonas spp. to horizontal gene transfer in Burkholderia spp. and Pectobacterium spp. DNA extracted from cereal crop rhizospheres and screened for the presence of phzF contained sequences consistent with the presence of a diverse population of phenazine producers in commercial farm fields located in central Washington state, which provided the first evidence of United States soils enriched in indigenous phenazine-producing bacteria.The naturally occurring phenazines include more than 50 nitrogen-containing heterocyclic pigments of bacterial origin (36). They have characteristic absorption spectra with two peaks in the UV range and at least one peak in the visible range that determines their colors (42). Almost all phenazines are broadly inhibitory to the growth of bacteria and fungi due to their ability to undergo cellular redox cycling in the presence of oxygen and reducing agents (including NADH and NADPH) and cause the accumulation of toxic superoxide and hydrogen peroxide (42). Phenazine-1-carboxylic acid (PCA), 2-hydroxyphenazine-1-carboxylic acid, and phenazine-1-carboxamide (PCN) produced in the rhizosphere by Pseudomonas fluorescens and Pseudomonas chlororaphis inhibit soilborne phytopathogenic fungi (13, 62) and contribute to the natural suppression of Fusarium wilt disease in certain soils in France (45). Phenazines produced by Pantoea agglomerans on apple flowers contribute to suppression of phytopathogenic Erwinia amylovora, which causes fire blight disease (22). Production of pyocyanin (PYO) by Pseudomonas aeruginosa is required for generation of disease symptoms in plants and killing of the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster (40, 54), and it is also critical for lung infection by P. aeruginosa in mice (35). In contrast, some phenazines produced by Streptomyces spp. are not cytotoxic in eukaryotes and have promise as anticancer or anti-infective drugs (36).In addition to the effects of phenazines on other organisms, recent studies have indicated that these compounds directly activate certain transcription factors and act as intercellular signals in P. aeru...

Section: Discussionmentioning

confidence: 99%

Diversity and Evolution of the Phenazine Biosynthesis Pathway

Peever

et al. 2010

Appl Environ Microbiol

233

231

Handbook of Anticancer Drugs From Marine Origin

“…On the basis of the precursor feeding experiments and in silico analysis of the biosynthetic genes, biosynthetic pathway for BU-4664L is proposed in which three precursor components are coupled to assemble this unique structure ( [27], Fig. 17.10).…”

Section: Bu-4664l a Cell Migration Inhibitor From Micromonospora Spmentioning

confidence: 99%

Antitumor Compounds from Actinomycetes in Deep-sea Water of Toyama Bay

Igarashi

2014

Actinomycetes are the richest source of bioactive small molecules with high structural complexity and diversity which have been an inspiration to drug development. After the intensive screening efforts from soil-derived actinomycetes over a half century, it became necessary to exploit new microbial resources for discovering new drug leads. The deep-sea water in Toyama Bay is known as the 'specific deep-sea water of Japan Sea' because Sea of Japan is almost enclosed from the Pacific Ocean and the water exchanges very slowly with the neighboring seas. Furthermore, high dissolved oxygen concentration in this sea water gives rise to high biological productivity. As a part of investigation on the deep-sea water in Toyama Bay, we undertook the isolation of actinomycetes from deep-sea water for evaluation of bioactive compound production. This chapter summarizes the chemistry and biology of antitumor compounds produced by actinomycetes collected from the deep-sea water in Toyama Bay.Keywords Actinomycetes · Micromonospora · Deep-sea water · Antitumor compounds IntroductionToyama Bay is located in the northern shores of Honshu, Japan, and faced to Sea of Japan. The sea water present deeper than 300 m is called 'deep-sea water', which occupies about 60 % of the total volume of Toyama Bay. The deep-sea water of Toyama Bay has a low temperature, annually stable around 2 °C. The salinity is also stable at 34.0-34.1 g/kg, higher than that of surface sea water (32-33 g/kg). Utilization of the deep-sea water is being studied for commercial/industrial purposes such as aquatic culture of cold-water shrimps. As a part of investigation on the deep-sea water in Toyama Bay, we undertook the isolation of actinomycetes from

“…13,35,68 Other examples are the tetrapetalones, 38 which were shown to incorporate an AHBA moiety, and diazepinomicin, which was also proposed to incorporate an AHBA-derived moiety, although final proof is still outstanding. 69 A particularly intriguing example are the saliniketals from Salinispora arenicola, which share a biosynthetic pathway with the rifamycins. 39 After the stage of 34a-deoxyrifamycin W, they diverge from the rifamycin pathway, undergoing an alternate cleavage of the polyketide chain, which ultimately leads to loss of the AHBA-derived moiety and the first two polyketide extension units, leaving only the AHBA nitrogen behind in the product.…”

Section: The Ahba Synthase Gene As a Probementioning

confidence: 99%

The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review

2010

The aminoshikimate pathway of formation of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of ansamycin and other antibiotics is reviewed. In this biosynthesis, genes for kanosamine formation have been recruited from other genomes, to provide a nitrogenous precursor. Kanosamine is then phosphorylated and converted by common cellular enzymes into 1-deoxy-1-imino-erythrose 4-phosphate, the substrate for the formation of aminoDAHP. This is converted via 5-deoxy-5-aminodehydroquinic acid and 5-deoxy-5-aminodehydroshikimic acid into AHBA. Remarkably, the pyridoxal phosphate enzyme AHBA synthase seems to have two catalytic functions: As a homodimer, it catalyzes the last reaction in the pathway, the aromatization of 5-deoxy-5-aminodehydroshikimic acid, and at the beginning of the pathway in a complex with the oxidoreductase RifL it catalyzes the transamination of UDP-3-keto-D-glucose. The AHBA synthase gene also serves as a useful tool in the genetic screening for new ansamycins and other AHBA-derived natural products.