Epoxide Hydrolase Lsd19 for Polyether Formation in the Biosynthesis of Lasalocid A: Direct Experimental Evidence on Polyene-Polyepoxide Hypothesis in Polyether Biosynthesis

Shichijo, Yoshihiro; Migita, Akira; Oguri, Hiroki; Watanabe, Masamichi; Tokiwano, Tetsuo; Watanabe, Kenji; Oikawa, Hideaki

doi:10.1021/ja8040543

Cited by 83 publications

(78 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the disruption of the lsd genes has not been succeeded, the enzymatic activity of the epoxide hydrolase Lsd19 was confirmed by in vitro formation of lasalocid from a synthesized bisepoxide through cascade epoxide opening reactions. 58 The whole gene cluster for echinomycin biosynthesis was cloned and expressed in E. coli, 59 which also confirmed the function of the echinomycin cluster on pKSL.…”

Section: Pksl In S Lasaliensismentioning

confidence: 56%

Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters

Kinashi

2010

J Antibiot

View full text Add to dashboard Cite

Many giant linear plasmids have been isolated from Streptomyces by using pulsed-field gel electrophoresis and some of them were found to carry an antibiotic biosynthetic cluster(s); SCP1 carries biosynthetic genes for methylenomycin, pSLA2-L for lankacidin and lankamycin, and pKSL for lasalocid and echinomycin. Accumulated data suggest that giant linear plasmids have played critical roles in genome evolution and horizontal transfer of secondary metabolism. In this review, I summarize typical examples of giant linear plasmids whose involvement in antibiotic production has been studied in some detail, emphasizing their finding processes and interaction with the host chromosomes. A hypothesis on horizontal transfer of secondary metabolism involving giant linear plasmids is proposed at the end.

show abstract

Section: Pksl In S Lasaliensismentioning

confidence: 56%

Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters

Kinashi

2010

J Antibiot

View full text Add to dashboard Cite

show abstract

“…Perhaps more biologically relevant is the epoxide hydrolase enzyme Lsd19 that has recently been reported to catalyze a 6-endo cyclization in the biosynthesis of lasolocid A (33). Although the class of natural products and the species that the enzyme originate from are different in this case compared with the ladder polyether natural products, there is nonetheless a striking parallelism between the role of the enzyme and the role that the combination of water and substrate play in the reactions discussed above.…”

Section: Implications For the Biogenisis Of The Ladder Polyether Naturalmentioning

confidence: 99%

Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

Byers

Jamison

2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Despite the myriad of selective enzymatic reactions that occur in water, chemists have rarely capitalized on the unique properties of this medium to govern selectivity in reactions. Here we report detailed mechanistic investigations of a water-promoted reaction that displays high selectivity for what is generally a disfavored product. A combination of structural and kinetic data indicates not only that synergy between substrate and water suppresses undesired pathways but also that water promotes the desired pathway by stabilizing charge in the transition state, facilitating proton transfer, doubly activating the substrate for reaction, and perhaps most remarkably, reorganizing the substrate into a reactive conformation that leads to the observed product. This approach serves as an outline for a general strategy of exploiting solvent-solute interactions to achieve unusual reactivity in chemical reactions. These findings may also have implications in the biosynthesis of the ladder polyether natural products, such as the brevetoxins and ciguatoxins.entropic control | biomimetic G iven its simple structure and low molecular weight, water is a remarkably complex substance. Several landmark investigations (1) have revealed the ability of water to self-assemble to form sophisticated dynamic hydrogen bond networks, which accounts for its unusual properties, such as its high boiling point and high surface tension (2). Despite the unique properties that it offers and that nature has exploited, water is generally eschewed in synthetic chemistry largely because of chemical incompatibility with many commonly used reagents and the low aqueous solubility of many organic molecules coupled with the attendant assumption that homogeneity is required for reactivity. Although several important examples of remarkable reactivity have been documented for reactions carried out in water (3-5), on the surface of water (6, 7), or in micelles suspended in water (8, 9), utilization of the "biological solvent" in organic reactions remains uncommon.We became acutely aware of the remarkable properties of water when we discovered that neutral aqueous solutions of epoxy alcohol 1a underwent a spontaneous and selective "endo" cyclization reaction to form 6,6-fused bicyclic product 2a (Fig. 1) (10-12). Exceptional reactivity and selectivity were observed only when two criteria were satisfied: The substrate contained a sixmembered tetrahydropyran ring, and the solvent used was water at pH 7.0. These surprising results were counter to a set of general empirical rules put forth by Baldwin for cyclization reactions, which state that the smaller ring product resulting from what is commonly called an exo cyclization is favored for similar reactions (13). The tetrahydropyranol ring, therefore, appeared to "template" the endo cyclization pathway to form the larger ring product with water playing a critical yet heretofore unknown role.Moreover, 2a is a substructure found in a large family of natural products commonly referred to as the ladder polyethers (e....

show abstract

“…, tetronomycin 86 and nigericin 87 . In the case of monensin 62,88 and lasalocid 63,89 , these EHs encoding genes have been expressed and the EH activity of the enzymes confirmed.…”

Section: Biosynthesis Of Lasalocidmentioning

confidence: 92%

“…More direct evidence of the involvement of an enzyme-catalyzed cascade of epoxide-opening reactions in the biosynthesis of polyether was provided by Oikawa in their study of lasalocid biosynthesis 63 . They analyzed biosynthetic genes of lasalocid, reavealing high homology of lsd19 to the putative EH genes monBI and monBII.…”

Section: Biosynthesis Of Lasalocidmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of an Epoxide Hydrolase from the Florida Red Tide Dinoflagellate, Karenia brevis

Sun¹

View full text Add to dashboard Cite

vi Inspired by Cane-Celmer-Wesley's proposal regarding monensin biosynthesis, Nakanishi and Shimizu proposed a biosynthetic pathway for brevetoxin which suggests that PKS-mediated synthesis of the polyene is followed by epoxidation to afford a polyepoxide which then undergoes an epoxide-opening cascade, catalyzed by an epoxide hydrolase (EH).To find evidence to support the hypothesis that an epoxide hydrolase from polyether ladder producing dinoflagellates will catalyze the construction of the polyether ladder framework from polyepoxide substrates, and to study the role of epoxide hydrolase in the biosynthesis of polyether ladder compounds, it is necessary to identify and produce one or more epoxide hydrolase from dinoflagellates. The methods to detect epoxide hydrolase activity in K. brevis and different techniques to obtain epoxide hydrolases from K. brevis are discussed. A microsomal EH identified from a K. brevis EST library was cloned and expressed. The characterization of this EH, including substrate selectivity and enantioselectivity as well as its potential to catalyze the critical ento-tet cyclization epoxy alcohol, is discussed.vii CONTENTS

show abstract

Epoxide Hydrolase Lsd19 for Polyether Formation in the Biosynthesis of Lasalocid A: Direct Experimental Evidence on Polyene-Polyepoxide Hypothesis in Polyether Biosynthesis

Cited by 83 publications

References 22 publications

Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters

Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters

Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

Characterization of an Epoxide Hydrolase from the Florida Red Tide Dinoflagellate, Karenia brevis

Contact Info

Product

Resources

About