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The active site quino-cofactor that has been proposed in the Aspergillus niger amine oxidase AO-I has been reassessed from properties of model compounds. The name 'catalytic chelator' is given to inhibitors that promote the release of the active-site zinc of ZnCPD. The antiarthritis drug D-penicillamine, D-PEN, differs from D-Cys by the presence of two methyl groups on the beta carbon. It inhibits ZnCPD by promoting the release. A possible D-PEN mechanism in arthritis and Wilson's disease is suggested. Complications in use of D-PEN may be partially explained

An aminobenzo(b)fluorene called stealthin C was synthesized, isolated from a Streptomyces murayamaensis culture and incorporated into kinamycin D. It was found to be a new intermediate in the biosynthesis of the benzo(b)fluorene antibiotic after analysis of a deuterated sample showed it to be specifically incorporated into kinamycin D. It is also postulated to be the hydroxylation substrate for the biosynthesis of stealthin A by S. viridochromogenes.

A pathway via condensation of a four-carbon unit from the tricarboxylic acid (TCA) cycle with a three-carbon unit, possibly phosphoenol pyruvate, was gleaned from the biosynthesis of 4-hydroxy-3-nitrosobenzamide in Streptomyces murayamaensis mutants MC2 and MC3 and therefore, of 3-amino-4-hydroxybenzoic acid. 3-Amino-4-hydroxy(5-2H)benzoic acid was readily incorporated into the ferrous chelate of 4-hydroxy-3-nitrosobenzamide by S. murayamaensis in the isolation of 4-hydroxy-3-nitrosobenzamide and its ferrous chelate from S. murayamaensis. The involvement of the TCA cycle and the orientation of the four-carbon intermediate was confirmed.

A mutant strain MC1 of Streptomyces murayamaensis, blocked in the mutagenic biosynthesis of kinamycins, yields kinafluorenone by acetylation in pyridine. Spectroscopic analysis shows that the colored metabolite has a molecular formula C25H20O8 and a benzo(b)fluorenone structure, the first such compound isolated from a natural source. It is formed at the nitrogen insertion step of the biosynthetic pathway. Bioassays of its triacetate show no detectable antibiotic activity.

3-Amino-4-hydroxybenzoic acid (4) had been identified as a specific precursor of 4-hydroxy-3-nitrosobenzamide, an iron-chelating metabolite isolated from Streptomyces murayamaensis. This suggests that 4 might be a proximate precursor for the mC7N unit of the manumycin antibiotics. Results of experiments conducted to verify this hypothesis showed that 4 is a precursor of the mC7N moiety of asukamycin, an antibiotic of the manumycin family.

Prekinamycin (Cpd A) belongs to the family of kinamycin antibiotics that lacks the oxidative capability in one ring. Syntheses of previously reported kinamycins showed that their structures are similar to that of 5-diazobenzo[b]fluorenes. A comparison of the structure of Cpd A isolated from Streptomyces murayamaensis and the structure of synthetic Cpd A, however, that the two have completely different structures, and therefore are different from each other. The structure of Cpd A was shown to match that of another prekinamycin, Cpd B.

Structural analysis of kinamycin antibiotics, initially isolated from Streptomyces murayamaensis and characterized as benzo(b)carbazoloquinone cyanamides, provides revised structures for them, establishing them as 5-diazobenzo(b)fluorenes. Prekinamycin is a diazo compound. Kinamycin biosynthesis may involve 5, or 12-deoxy-10 or 7-O-dimethyl-9 as intermediates.

Reports on the biosynthesis of 4-hydroxy-3-nitrosobenzamide in Streptomyces murayamaensis mutants MC2 and MC using sodium [1,2-13C2]- and [1-13C,18O2]acetate, sodium [2,3-13C2]succinate, [1,2-13C2]glutamic acid, [4,13C]aspartic acid, and sodium [1-13C]- and [2,3-13C2]pyruvate. Subsequent specific incorporations of acids.

Aim: To test efficacy and durability of a polyphenol-based prebiotic treatment for acute gastroenteritis in a 300 patient double-blinded clinical study., Methods: A two-arm randomized, double-blinded, placebo-controlled clinical study was conducted at two public health centers in Managua, Nicaragua. Potential subjects who qualified based on inclusion and exclusion criteria were randomly assigned to one of two treatment arms. Two thirds of the subjects (n = 200) received a single titrated 0.5-2 ounce liquid dose of a novel polyphenol-based prebiotic (Aliva(TM)) diluted with 2 to eight ounces of oral rehydration solution (ORS). One third of the subjects (n = 100) were randomized to receive two liquid ounces of a taste and color-matched placebo diluted in eight ounces of ORS. The outcome variables measured included stool consistency, stomach discomfort, gas and bloating, and heartburn/indigestion. The study subjects ranked their stool consistency and the severity of their subjective symptoms at specified intervals from immediately prior to treatment, to five days post treatment. All subjects recorded their symptoms in a study diary. The study subjects also recorded the time and consistencies of all stools in their study diary. Stool consistency was compared to the picture and descriptions on the Bristol Stool Chart, and any stool rated greater than Type 4 was considered unformed. The clinical study team reviewed the study diaries with subjects during daily follow-up calls and close-out visits, and recorded the data in case report forms., Results: After receiving a single dose, Aliva treated subjects reported shorter median time to their last unformed stool (1 h 50 min) than placebo treated subjects (67 h 50 min.), a statistically significant difference [95%CI: -3178-(-2018), P = 0.000]. Aliva treated subjects also reported shorter median their time to last unformed stool (TTLUS) (1 hrs 50 min) than placebo treated subjects (67 h 50 min), which was also a statistically significant difference (P = 0.000).The percentage of subjects recording TTLUS was greater for those who received Aliva vs placebo at 30 min (P = 0.027), 2 h (P = 0.000), 24 h (P = 0.000), 48 h (P = 0.000), 72 h (P = 0.000), and 5 d (P = 0.000) post dose. There were 146 study subjects 14 years old or older, which was the criteria set for reliable self-reporting of subjective symptoms. Of those 146 subjects, 142 reported stomach pain and discomfort during screening. From 90 minutes [95%CI: -1.8-(-0.01), P = 0.048] through 5 d [95%CI: -3.4-(-1.9), P = 0.000), the subjects treated with Aliva experienced significantly less stomach pain and discomfort than those who received placebo. Of those same 146 participants, 114 subjects reported gas and bloating during screening. Similarly, subjects who received Aliva experienced significantly less gas and bloating from 2 h [95%CI: -1.7-(-0.39), P = 0.030] through 5 d (95%CI: -2.0-0.42, P = 0.005) compared with the placebo arm., Conclusion: In this double-blind, randomized clinical study, subjects with acute gastroenteritis receiving Aliva prebiotic showed significant and sustained improvement of multiple symptoms vs those receiving placebo.