Convergent strategies in biosynthesis

Dairi, Tohru; Kuzuyama, Tomohisa; Nishiyama, Makoto; Fujii, Isao

doi:10.1039/c0np00047g

Cited by 38 publications

(27 citation statements)

References 270 publications

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“…Several complete convergent biosynthetic pathways, which account for many missing genes, have been reported (reviewed by Dairi et al 2011). From a chemotaxonomic point-of-view, the convergent biosynthesis of the menaquinones (MK) stands-out and therefore it is analysed in further detail.…”

Section: Evolutionary Implications Of Gsmrsmentioning

confidence: 99%

What can genome-scale metabolic network reconstructions do for prokaryotic systematics?

Barona‐Gómez

Cruz-Morales

Noda‐Garcia

2011

Antonie van Leeuwenhoek

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It has recently been proposed that in addition to Nomenclature, Classification and Identification, Comprehending Microbial Diversity may be considered as the fourth tenet of microbial systematics [Staley JT (2010) The Bulletin of BISMiS, 1(1): 1-5]. As this fourth goal implies a fundamental understanding of microbial speciation, this perspective article argues that translation of bacterial genome sequences into metabolic features may contribute to the development of modern polyphasic taxonomic approaches. Genome-scale metabolic network reconstructions (GSMRs), which are the result of computationally predicted and experimentally confirmed stoichiometric matrices incorporating all enzyme and metabolite components encoded by a genome sequence, provide a platform that can illustrate bacterial speciation. As the topology and the composition of GSMRs are expected to be the result of adaptive evolution, the features of these networks may provide the prokaryotic taxonomist with novel tools for reaching the fourth tenet of microbial systematics. Through selected examples from the Actinobacteria, which have been inferred from GSMRs and experimentally confirmed after phenotypic characterisation, it will be shown that this level of information can be incorporated into modern polyphasic taxonomic approaches. In conclusion, three specific examples are illustrated to show how GSMRs will revolutionize prokaryotic systematics, as has previously occurred in many other fields of microbiology.

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Section: Evolutionary Implications Of Gsmrsmentioning

confidence: 99%

What can genome-scale metabolic network reconstructions do for prokaryotic systematics?

Barona‐Gómez

Cruz-Morales

Noda‐Garcia

2011

Antonie van Leeuwenhoek

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“…The classic biosynthetic pathway of 374 involves eight steps starting from chorismate. 262 Dairi and coworkers discovered an alternative chorismate-derived pathway to menaquinone biosynthesis, named the futalosine pathway (Scheme 51). 263 Futalosine ( 368 ) is converted to dehypoxanthine futalosine (DHFL, 369 ) by the hydrolase MqnB, followed by a C-C coupling step that affords cyclic-DHFL (CDHFL, 372 ) by the radical SAM enzyme MqnC.…”

Section: Radical Cyclization Mechanismsmentioning

confidence: 99%

Oxidative Cyclization in Natural Product Biosynthesis

et al. 2016

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Oxidative cyclizations are important transformations that occur widely during natural product biosynthesis. The transformations from acyclic precursors to cyclized products can afford morphed scaffolds, structural rigidity and biological activities. Some of the most dramatic structural alterations in natural product biosynthesis occur through oxidative cyclization. In this review, we examine the different strategies used by Nature to create new intra-(inter-)-molecular bonds via redox chemistry. The review will cover both oxidation- and reduction-enabled cyclization mechanisms, with an emphasis on the former. Radical cyclizations catalyzed by P450, nonheme iron, α-KG dependent oxygenases and radical SAM enzymes are discussed to illustrate the use of molecular oxygen and S-adenosylmethionine to forge new bonds at unactivated sites via one-electron manifolds. Nonradical cyclizations catalyzed by flavin-dependent monooxygenases and NAD(P)H-dependent reductases are covered to show the use of two-electron manifolds in initiating cyclization reactions. The oxidative installation of epoxides and halogens into acyclic scaffolds to drive subsequent cyclizations are separately discussed as examples of “disappearing” reactive handles. Lastly, oxidative rearrangement of rings systems, including contractions and expansions will be covered.

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“…In the recently discovered futalosine-dependent pathway (17)(18)(19)(20), MqnE catalyzes the conversion of 40 to aminofutalosine (41) (21). A mechanistic proposal is outlined in Fig.…”

Section: Futalosine-dependent Menaquinone Biosynthesis (Mqnc and Mqne)mentioning

confidence: 99%

Radical S-Adenosylmethionine (SAM) Enzymes in Cofactor Biosynthesis: A Treasure Trove of Complex Organic Radical Rearrangement Reactions

Mehta

Abdelwahed

Mahanta

et al. 2015

Journal of Biological Chemistry

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In this minireview, we describe the radical S-adenosylmethionine enzymes involved in the biosynthesis of thiamin, menaquinone, molybdopterin, coenzyme F 420 , and heme. Our focus is on the remarkably complex organic rearrangements involved, many of which have no precedent in organic or biological chemistry. Radical S-adenosylmethionine (SAM)2 enzymes are among the most intriguing enzymes discovered over the past 15 years. In these enzymes, reduction of SAM by a 1ϩ cluster generates the adenosyl radical, which then abstracts a hydrogen atom from the substrate. The resulting substrate radical usually undergoes a rearrangement or fragmentation reaction to give the product radical (1). Sequence analysis suggests that a large number of enzymes use the radical SAM catalytic motif (2). We are still at an early stage of defining the catalytic mechanisms and the structural enzymology of this fascinating enzyme family.This minireview focuses on the organic chemistry of the radical SAM enzymes involved in cofactor biosynthesis: thiamin (1), F 0 (2), menaquinone (3), molybdopterin (4), and heme (5) (Fig. 1). (Biotin and lipoic biosynthesis also uses radical SAM enzymology and is covered separately in another minireview in this series (42).) In contrast to iron(IV)-oxo-derived radicals, where the dominant chemistry involves radical recombination with the iron-bound oxygen (P 450 rebound rate of Ͼ10 10 s Ϫ1 ) (3), radicals formed by hydrogen atom transfer to the 5Ј-deoxyadenosyl (5Ј-dA) radical are more persistent because the reverse reaction is relatively slow. This allows time for complex rearrangements to occur. Radical SAM enzymes catalyze a remarkable range of reactions due to the high intrinsic reactivity of organic radicals, which can undergo rapid hydrogen atom abstraction, double-bond addition, and fragmentation reactions as shown in Fig. 2. Prokaryotic Thiamin Pyrimidine Synthase (ThiC)Thiamin pyrophosphate (1) is an important cofactor in carbohydrate metabolism and branched chain amino acid biosynthesis, where it plays a key role in stabilization of the acyl carbanion biosynthon. The thiamin pyrimidine synthase (ThiC) catalyzes the conversion of aminoimidazole ribotide (AIR; 6) to hydroxymethylpyrimidine phosphate (HMP-P; 8) (Fig. 3A) (4, 5). The origin of all of the atoms of the product and the fate of all of the atoms of the substrate have been determined using isotope labeling studies (6 -8). This rearrangement, as far as we can tell, is the most complex unsolved rearrangement in primary metabolism.A mechanistic proposal for this reaction is shown in Fig. 3B (5). In this proposal, radical 7 abstracts a hydrogen atom from 6 to form 10. A ␤-scission followed by N-glycosyl bond cleavage gives 12. Electrophilic addition to the aminoimidazole followed by hydrogen atom transfer gives 14. The regenerated 5Ј-dA radical (7) abstracts a hydrogen atom from 14 to form 15. Radical addition to the imine followed by ␤-scission gives 17. A second ␤-scission followed by a diol dehydratase-like rearrangement gives 20 and 21. Ra...

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Convergent strategies in biosynthesis

Cited by 38 publications

References 270 publications

What can genome-scale metabolic network reconstructions do for prokaryotic systematics?

What can genome-scale metabolic network reconstructions do for prokaryotic systematics?

Oxidative Cyclization in Natural Product Biosynthesis

Radical S-Adenosylmethionine (SAM) Enzymes in Cofactor Biosynthesis: A Treasure Trove of Complex Organic Radical Rearrangement Reactions

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