β-Lactone Synthetase Found in the Olefin Biosynthesis Pathway

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2016 Dec 29

PMID 28029240

Citations 20

Authors

James K Christenson

Jack E Richman

Matthew R Jensen

Jennifer Y Neufeld

Carrie M Wilmot

Lawrence P Wackett

Affiliations

Soon will be listed here.

Abstract

The first β-lactone synthetase enzyme is reported, creating an unexpected link between the biosynthesis of olefinic hydrocarbons and highly functionalized natural products. The enzyme OleC, involved in the microbial biosynthesis of long-chain olefinic hydrocarbons, reacts with syn- and anti-β-hydroxy acid substrates to yield cis- and trans-β-lactones, respectively. Protein sequence comparisons reveal that enzymes homologous to OleC are encoded in natural product gene clusters that generate β-lactone rings, suggesting a common mechanism of biosynthesis.

Citing Articles

Fatty acyl-AMP ligases in bacterial natural product biosynthesis.

Liong A, Leao P Nat Prod Rep. 2025; .

PMID: 39968878 PMC: 11837247. DOI: 10.1039/d4np00073k.

Alligamycin A, an antifungal β-lactone spiroketal macrolide from Streptomyces iranensis.

Yang Z, Qiao Y, Strobech E, Morth J, Walther G, Jorgensen T Nat Commun. 2024; 15(1):9259.

PMID: 39461983 PMC: 11513958. DOI: 10.1038/s41467-024-53695-3.

Acetyl-CoA synthetase activity is enzymatically regulated by lysine acetylation using acetyl-CoA or acetyl-phosphate as donor molecule.

Qin C, Graf L, Striska K, Janetzky M, Geist N, Specht R Nat Commun. 2024; 15(1):6002.

PMID: 39019872 PMC: 11255334. DOI: 10.1038/s41467-024-49952-0.

Cryptic enzymatic assembly of peptides armed with β-lactone warheads.

Xu G, Torri D, Cuesta-Hoyos S, Panda D, Yates L, Zallot R Nat Chem Biol. 2024; 20(10):1371-1379.

PMID: 38951647 PMC: 11427300. DOI: 10.1038/s41589-024-01657-7.

Recombinant Expression and Purification of Large Bacterial Multienzyme Assemblies for Biosynthetic Processes.

Christenson J Methods Mol Biol. 2022; 2487:1-13.

PMID: 35687226 DOI: 10.1007/978-1-0716-2269-8_1.

References

Sukovich D, Seffernick J, Richman J, Gralnick J, Wackett L . Widespread head-to-head hydrocarbon biosynthesis in bacteria and role of OleA. Appl Environ Microbiol. 2010; 76(12):3850-62. PMC: 2893475. DOI: 10.1128/AEM.00436-10. View

Hemmerling F, Hahn F . Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides. Beilstein J Org Chem. 2016; 12:1512-50. PMC: 4979870. DOI: 10.3762/bjoc.12.148. View

Bonnett S, Papireddy K, Higgins S, del Cardayre S, Reynolds K . Functional characterization of an NADPH dependent 2-alkyl-3-ketoalkanoic acid reductase involved in olefin biosynthesis in Stenotrophomonas maltophilia. Biochemistry. 2011; 50(44):9633-40. DOI: 10.1021/bi201096w. View

Rachid S, Huo L, Herrmann J, Stadler M, Kopcke B, Bitzer J . Mining the cinnabaramide biosynthetic pathway to generate novel proteasome inhibitors. Chembiochem. 2011; 12(6):922-31. DOI: 10.1002/cbic.201100024. View

Kancharla P, Bonnett S, Reynolds K . Stenotrophomonas maltophilia OleC-Catalyzed ATP-Dependent Formation of Long-Chain Z-Olefins from 2-Alkyl-3-hydroxyalkanoic Acids. Chembiochem. 2016; 17(15):1426-9. DOI: 10.1002/cbic.201600063. View

Frias J, Richman J, Erickson J, Wackett L . Purification and characterization of OleA from Xanthomonas campestris and demonstration of a non-decarboxylative Claisen condensation reaction. J Biol Chem. 2011; 286(13):10930-8. PMC: 3064148. DOI: 10.1074/jbc.M110.216127. View

Bai T, Zhang D, Lin S, Long Q, Wang Y, Ou H . Operon for biosynthesis of lipstatin, the Beta-lactone inhibitor of human pancreatic lipase. Appl Environ Microbiol. 2014; 80(24):7473-83. PMC: 4249243. DOI: 10.1128/AEM.01765-14. View

Wyatt M, Ahilan Y, Argyropoulos P, Boddy C, Magarvey N, Harrison P . Biosynthesis of ebelactone A: isotopic tracer, advanced precursor and genetic studies reveal a thioesterase-independent cyclization to give a polyketide β-lactone. J Antibiot (Tokyo). 2013; 66(7):421-30. DOI: 10.1038/ja.2013.48. View

Albro P, DITTMER J . The biochemistry of long-chain, nonisoprenoid hydrocarbons. I. Characterization of the hydrocarbons of Sarcina lutea and the isolation of possible intermediates of biosynthesis. Biochemistry. 1969; 8(1):394-404. DOI: 10.1021/bi00829a055. View

10.

Feling R, Buchanan G, Mincer T, Kauffman C, Jensen P, Fenical W . Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora. Angew Chem Int Ed Engl. 2003; 42(3):355-7. DOI: 10.1002/anie.200390115. View

11.

Zhao C, Coughlin J, Ju J, Zhu D, Wendt-Pienkowski E, Zhou X . Oxazolomycin biosynthesis in Streptomyces albus JA3453 featuring an "acyltransferase-less" type I polyketide synthase that incorporates two distinct extender units. J Biol Chem. 2010; 285(26):20097-108. PMC: 2888422. DOI: 10.1074/jbc.M109.090092. View

12.

Dick L, Cruikshank A, Grenier L, Melandri F, Nunes S, Stein R . Mechanistic studies on the inactivation of the proteasome by lactacystin: a central role for clasto-lactacystin beta-lactone. J Biol Chem. 1996; 271(13):7273-6. DOI: 10.1074/jbc.271.13.7273. View

13.

Masamune S, Hayase Y, Chan W, Sobzak R . Tylonolide hemiacetal, the aglycone of tylosin, and its partial synthesis. J Am Chem Soc. 1976; 98(24):7874-5. DOI: 10.1021/ja00440a096. View

14.

Conti E, Franks N, Brick P . Crystal structure of firefly luciferase throws light on a superfamily of adenylate-forming enzymes. Structure. 1996; 4(3):287-98. DOI: 10.1016/s0969-2126(96)00033-0. View

15.

Frias J, Richman J, Wackett L . C29 olefinic hydrocarbons biosynthesized by Arthrobacter species. Appl Environ Microbiol. 2009; 75(6):1774-7. PMC: 2655437. DOI: 10.1128/AEM.02547-08. View