Microbial β‐lactone natural products

Microbial b-lactone natural products An annotated selection of World Wide Web sites relevant to the topics in microbial biotechnology. Obafluorin is an antimicrobial b-lactone compound produced by the bacterium Pseudomonas fluorescens. In this study, the compound was synthesized, analysed chemically and tested for biological activity. The triedimycins are a class of spiro b-lactones. They are not potent as antibiotics but show substantial in vitro antitumor activity against murine leukaemia cells. b-Lactone natural products inactivate homoserine transacetylase The b-lactone ebelactone A served as a lead compound to find potent inhibitors that inactivated homoserine transacetylase. Inhibition against that enzyme makes for a useful antimicrobial substance against pathogens, such as Haemophilus influenzae. This commercial website contains useful information on the b-lactone antibiotic and antifungal agent, (R,R)-hymeglusin. This patent builds off a knowledge of b-lactone natural products. Novel hydrophobic b-lactone structures with alkenyl, alkynyl and phenyl groups were synthesized to test as novel antimicrobial substances. Methylene-substituted b-lactones are intermediates in the synthesis of mimics of b-lactone natural products. The general characteristics of a simple methylene b-lac-tone are available here. Tetrahydrolipstatin is a b-lactone antiobesity drug, currently available with or without prescription. The Pub-chem website for this compound has information on chemical properties, biological assays and commercial availability. Lipstatin is the b-lactone natural product produced by a Streptomyces species that can be reduced to make the drug tetrahydrolipstatin. The patent was filed to protect certain aspects of the fermentative production of the compound. b-Lactones as synthetic intermediates for natural products The b-lactone functional group is described here in this thesis for its value in the synthesis of natural products. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Triene b-lactone antibiotics: Triedimycins https://www.ncbi.nlm.nih.gov/pubmed/1903377 The triedimycins are a class of spiro b-lactones. They are not potent as antibiotics but show substantial in vitro antitumor activity against murine leukaemia cells.
b-Lactone natural products inactivate homoserine transacetylase http://www.nature.com/ja/journal/v64/n7/abs/ja201137a.html The b-lactone ebelactone A served as a lead compound to find potent inhibitors that inactivated homoserine transacetylase. Inhibition against that enzyme makes for a useful antimicrobial substance against pathogens, such as Haemophilus influenzae.
b-Lactones as antibacterial agents: Patents https://www.google.com/patents/EP2254574A1?cl=en This patent builds off a knowledge of b-lactone natural products. Novel hydrophobic b-lactone structures with alkenyl, alkynyl and phenyl groups were synthesized to test as novel antimicrobial substances.

4-Methylene oxetanone
http://webbook.nist.gov/cgi/cbook.cgi?ID=C674828&Ma sk=8 Methylene-substituted b-lactones are intermediates in the synthesis of mimics of b-lactone natural products. The general characteristics of a simple methylene b-lactone are available here.
(-)-Lipstatin: Pubchem https://pubchem.ncbi.nlm.nih.gov/compound/71749817 Tetrahydrolipstatin is a b-lactone antiobesity drug, currently available with or without prescription. The Pubchem website for this compound has information on chemical properties, biological assays and commercial availability.
Fermentative production of lipstatin: Patent https://www.google.com/patents/EP2019869A1?cl=en Lipstatin is the b-lactone natural product produced by a Streptomyces species that can be reduced to make the drug tetrahydrolipstatin. The patent was filed to protect certain aspects of the fermentative production of the compound.
b-Lactones as synthetic intermediates for natural products http://oaktrust.library.tamu.edu/handle/1969.1/ETD-TAMU-2011-12-10494 The b-lactone functional group is described here in this thesis for its value in the synthesis of natural products. (2017) 10(1) Many of the natural products are not themselves b-lactones, but the versatile reactivity of b-lactones makes them useful as synthetic vehicles.
Omuralide: Pubchem https://pubchem.ncbi.nlm.nih.gov/compound/Omuralide #section=Top Omuralide has a b-lactone ring fused to a second fivemembered ring. The compound has been shown to inhibit cysteine endopeptidases. This study shows that minor structural differences can have a large impact on the biological targets of b-lactone natural products.

Synthesis of the proteasome inhibitors salinosporamide A, omuralide and lactacystin
Proteosome mutant in complex with omuralide http://www.rcsb.org/pdb/explore.do?structureId=4r00 This link is to a Protein DataBank page. The depositors conducted a study on the binding of different drugs to a yeast mutant proteosome, and one of the compounds tested was the b-lactone omuralide. This natural product is produced by a marine bacterium. It contains a c-lactam-b-lactone bicyclic core structure. It is being used in early stage clinical trials to treat myeloma. b-Lactone inhibitors of fatty acid synthase https://www.ncbi.nlm.nih.gov/pubmed/18710210 In this study, the hydrophobic b-lactone natural products with alkyl chains were used as models for synthesizing 28 novel congeners to test for biological activity. This study combined chemical synthesis and metabolic engineering to generate a series of salinosporamide analogues. Salinosporamide is natural product b-lactone produced by a marine bacterium that acts a proteosome inhibitor. Obafluorin produced by Pseudomonas fluorescens https://www.jstage.jst.go.jp/article/antibiotics1968/37/7/ 37_7_802/_article This is the original paper describing the discovery of the b-lactone natural product obafluorin.
Distribution of b-lactam and b-lactone producing bacteria https://www.ncbi.nlm.nih.gov/pubmed/7174535 This broadscale screening study, conducted in the pregenomic era, discovered a large number of b-lactam and b-lactone natural products produced by soil bacteria.