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G. David Novelli

Other affiliations: University of Texas at Austin
Bio: G. David Novelli is an academic researcher from Harvard University. The author has contributed to research in topics: Coenzyme A & Cofactor. The author has an hindex of 12, co-authored 13 publications receiving 1018 citations. Previous affiliations of G. David Novelli include University of Texas at Austin.

Papers
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TL;DR: Attempts to identify this “activator” function of microbial extracts led to the proposition that the phosphate exchange and arsenolysis system may be responsible for the acetyl transfer from acetyl phosphate.

473 citations

Journal ArticleDOI
TL;DR: The coenzyme content was followed throughout the purification by the assay method described in a preceding paper (2), and hog liver was found most suitable.

75 citations


Cited by
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TL;DR: The concept of photochemical sterilization was introduced in this article, where microorganisms were killed photoelectrochemically with semiconductor powder (platinum-loaded titanium oxide, TiO2/Pt).
Abstract: We report the novel concept of photochemical sterilization. Microbial cells were killed photoelectrochemically with semiconductor powder (platinum-loaded titanium oxide, TiO2/Pt). Coenzyme A, (CoA) in the whole cells was photo-electrochemically oxidized and, as a result, the respiration of cells was inhibited. Inhibition of respiratory activity caused death of the cells. Lactobacillus acidophilus, Saccharomyces cerevisiae and Escherichia coli (103 cells/ml respectively) were completely sterilized when they were incubated with TiO2/Pt particles under metal halide lamp irradiation for 60–120 min.

1,317 citations

Journal ArticleDOI
TL;DR: This Review will begin by summarizing unifying features of radical SAM enzymes, and in subsequent sections delve further into the biochemical, spectroscopic, structural, and mechanistic details for those enzymes that catalyze an amazingly diverse set of reactions.
Abstract: It was once widely held that nearly all reactions in biology were catalyzed via mechanisms involving paired electron species. Beginning approximately 40 years ago, this paradigm was repeatedly challenged as examples of enzymatic reactions involving organic radical intermediates began to emerge, and it is now well accepted that biochemical reactions often involve organic radicals. Indeed, some of the most intensely studied metalloenzymes, including cytochrome P450, methane monooxygenase, ribonucleotide reductase, and the adenosylcobalamin (B12) enzymes, catalyze reactions employing organic radical intermediates. As a general rule, enzymes utilizing radical mechanisms catalyze reactions that would be difficult or impossible to catalyze by polar mechanisms, most often involving H-atom abstraction from an unactivated C–H bond. Among the more recent additions to the enzymes that catalyze radical reactions are the radical S-adenosylmethionine (radical SAM) enzymes, which were first classified as a superfamily in 2001.1 These enzymes utilize a [4Fe–4S] cluster and SAM to initiate a diverse set of radical reactions, in most or all cases via generation of a 5′-deoxyadenosyl radical (dAdo•) intermediate. Although 2001 marked the identification of this superfamily largely through bioinformatics, the discovery of iron metalloenzymes utilizing SAM to initiate radical reactions precedes this date by more than a decade. For example, early studies on the activation of pyruvate formate-lyase showed that it involved the generation of a stable protein radical,2 and was stimulated by the presence of iron, SAM, and an “activating component” from the cell extract now known to be the pyruvate-formate lyase activating enzyme (PFL-AE).3 The radical on PFL was ultimately shown to be located on a specific glycine residue,4 and was one of the first stable protein radicals characterized. PFL-AE was ultimately shown to contain a catalytically essential iron–sulfur cluster,5 and to use SAM as an essential component of PFL activation.6 The anaerobic ribonucleotide reductase, similar to PFL, contains a stable glycyl radical that was shown in early work to require an iron–sulfur cluster and SAM for activation.7 Likewise, preliminary investigations on lysine 2,3-aminomutase (LAM) published in 1970 demonstrated activation by ferrous ion and a strict requirement for SAM.8 Like PFL-AE, LAM was ultimately found to contain a catalytically essential iron–sulfur cluster.9 Work in Perry Frey’s lab showed that LAM used the adenosyl moiety of SAM to mediate hydrogen transfer in a manner similar to adenosylcobalamin-dependent rearrangements, implicating radical intermediates.10 Biotin synthase was first reported to require iron and SAM in 1995,11 and was subsequently shown to contain iron–sulfur clusters and to catalyze a radical reaction.12 These four enzyme systems (PFL/PFL-AE, aRNR, LAM, and biotin synthase) provided early indications of a new type of biological cofactor consisting of an iron–sulfur cluster and SAM, which initiate radical reactions using a fundamental new mechanism of catalysis.13 What none of us in the field in the early days probably anticipated, however, was just how ubiquitous these enzymes would turn out to be. The initial report of the superfamily by Sofia et al. identified ∼600 members;1 however, now that number is ∼48 100 members.14 These enzymes are found across the phylogenetic kingdom and catalyze an amazingly diverse set of reactions, the vast majority of which have yet to be characterized. This Review will begin by summarizing unifying features of radical SAM enzymes, and in subsequent sections delve further into the biochemical, spectroscopic, structural, and mechanistic details for those enzymes that have been characterized. In most cases, these enzymes are grouped by reaction type; however, in two cases (syntheses of modified tetrapyrroles and complex metal cluster cofactors), we have chosen to group together several radical SAM enzymes that catalyze different reaction types but which act together in the same or related metabolic pathways.

582 citations

Journal ArticleDOI
TL;DR: Attempts to identify this “activator” function of microbial extracts led to the proposition that the phosphate exchange and arsenolysis system may be responsible for the acetyl transfer from acetyl phosphate.

473 citations