This work describes the relationship between the antibacterial activity and the ester chain length (C1-C8) of (R)-3-Hydroxybutyric ((R)-3-HB) alkyl esters that synthesized from (R)-3-HB acid ((R)-3-HBA) by esterification reaction. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) decrease as the length of the (R)-3-HB alkyl ester chain increases from 1 to 6, but (R)-3-HB-C7 and (R)-3-HB-C8 have their own rules for different microorganisms. Among them, the (R)-3HB-C6 has the relatively best antibacterial and antifungal properties, which MIC were 1.95 mg mL−1 against E. coli and S. aureus; 0.98 mg mL−1 against C. albicans and B. subtilis; 0.49 mg mL−1 against A. niger. Finally, the antimicrobial mechanisms of the (R)-3HB-C6 are revealed, and these include disruption of biofilm and the bacterial wall/membrane, leakage of the intracellular content, and change in the transmembrane potential. These results imply the potential application of (R)-3-HB alkyl ester as new antimicrobial agents; future research can use this as an antibacterial element to synthesize new polymer materials or agents with high-efficiency antibacterial activity.
De CellesMDSalomonJMarinierA, et al.Identifying more epidemic clones during a hospital outbreak of multidrug-resistant acinetobacter baumannii. Plos One2012; 7(9): 8.
2.
MakaryMAKaczmarskiKNachmanK. A call for doctors to recommend antibiotic-free foods: agricultural antibiotics and the public health crisis of antimicrobial resistance. J Antibiot2018; 71(8): 685–687.
3.
MeiLLuZTZhangXG, et al.Polymer-Ag nanocomposites with enhanced antimicrobial activity against bacterial infection. Acs Appl Mater Inter2014; 6(18): 15813–15821.
4.
ZhangQMaPCXieJY, et al.Host defense peptide mimicking poly--peptides with fast, potent and broad spectrum antibacterial activities. Biomater Sci2019; 7(5): 2144–2151.
5.
XieGGaoSOuJ, et al.Conjugating peptides onto 1D Rodlike bionanoparticles for enhanced activity against gram-negative bacteria. Nano Lett2021; 21(4): 1722–1728.
YangYCCaiZGHuangZH, et al.Antimicrobial cationic polymers: from structural design to functional control. Polym J2018; 50(1): 33–44.
8.
XiJQAnLFHuangYL, et al.Ultrasmall FeS2 nanoparticles-decorated carbon spheres with laser-mediated ferrous ion release for antibacterial therapy. Small2021; 17(13): 12.
9.
MeenakshisundaramIKalimuthuSPriyaPG, et al.Facile green synthesis and antimicrobial performance of Cu2O nanospheres decorated g-C3N4 nanocomposite. Mater Res Bull2019; 112: 331–335.
10.
WangADuanSDingX, et al.Bioswitchable antibacterial coatings enable self‐sterilization of implantable healthcare dressings. Advanced Functional Materials31: 18, 2021.
11.
BhushanMMohapatraDKumarY, et al.Fabrication of novel bioceramic alpha-Fe2O3/MnO nanocomposites: study of their structural, magnetic, biocompatibility and antibacterial properties. Mater Sci Eng B-Advanced Funct Solid-State Mater2021; 268: 12746.
12.
GrigorasAG. Natural and synthetic polymeric antimicrobials with quaternary ammonium moieties: a review. Environ Chem Lett 2021; 14.
13.
XueYXiaoHNZhangY. Antimicrobial polymeric materials with quaternary ammonium and Phosphonium Salts. Int J Mol Sci2015; 16(2): 3626–3655.
14.
Martinez-CarballoESitkaAGonzalez-BarreiroC, et al.Determination of selected quaternary ammonium compounds by liquid chromatography with mass spectrometry. Part I. Application to surface,) waste and indirect discharge water samples in Austria. Environ Pollut2007; 145(2): 489–496.
15.
Van de VoordeALorgeouxCGromaireMC, et al.Analysis of quaternary ammonium compounds in urban stormwater samples. Environ Pollut2012; 164: 150–157.
16.
Pateiro-MoureMArias-EstevezMSimal-GandaraJ. Critical review on the environmental fate of quaternary ammonium herbicides in soils devoted to vineyards. Environ Sci Technol2013; 47(10): 4984–4998.
17.
ClaraMScharfSScheffknechtC, et al.Occurrence of selected surfactants in untreated and treated sewage. Water Res2007; 41(19): 4339–4348.
18.
TandukarMOhSTezelU, et al.Long-term exposure to benzalkonium chloride disinfectants results in change of microbial community structure and increased antimicrobial resistance. Environ Sci Technol2013; 47(17): 9730–9738.
19.
SimoncicBTomsicB. Structures of novel antimicrobial agents for textiles - a review. Text Res J2010; 80(16): 1721–1737.
20.
GuilhelmelliFVilelaNAlbuquerqueP, et al.Antibiotic development challenges: the various mechanisms of action of antimicrobial peptides and of bacterial resistance. Front Microbiol2013; 4: 12.
DawesEASeniorPJ. The role and regulation of energy reserve polymers in micro-organisms. Adv Microbial Physiology1973; 10: 135–266.
23.
ChenGQPatelMK. Plastics derived from biological sources: present and future: a technical and environmental review. Chem Rev2012; 112(4): 2082–2099.
24.
AsranASRazghandiKAggarwalN, et al.Nanofibers from blends of polyvinyl alcohol and polyhydroxy butyrate as potential scaffold material for tissue engineering of skin. Biomacromolecules2010; 11(12): 3413–3421.
25.
KamachiMZhangSMGoodwinS, et al.Enzymatic polymerization and characterization of new poly(3-hydroxyalkanoate)s by a bacterial polymerase. Macromolecules2001; 34(20): 6889–6894.
26.
SeebachDChowHFJacksonRFW, et al.(+)-11,11'-DI-O-METHYLELAIOPHYLIDENE - PREPARATION FROM ELAIOPHYLIN AND TOTAL SYNTHESIS FROM (R)-3-HYDROXYBUTYRATE AND (S)-MALATE. Liebigs Annalen Der Chem1986; 7: 1281–1308.
27.
SeebachDHerrmannGFLengweilerUD, et al.Synthesis and enzymatic degradation of dendrimers from (R)-3-hydroxy-butanoic acid and trimesic acid. Angew Chem-int Edit Engl1996; 35(23–24): 2795–2797.
28.
ChibaTNagatsumaMNakaiT. A FACILE, STEREOCONTROLLED ENTRY TO KEY INTERMEDIATES FOR THIENAMYCIN SYNTHESIS FROM ETHYL (S)-3-HYDROXYBUTANOATE. Chem Lett1985; 9: 1343–1346.
29.
SeebachDAlbertMArvidssonPI, et al.From the biopolymer PHB to biological investigations of unnatural beta- and gamma-peptides. Chimia2001; 55(4): 345–353.
LeeSYLeeY. Metabolic engineering of escherichia coli for production of enantiomerically pure (R)-(-)-hydroxycarboxylic acids. Appl Environ Microbiol2003; 69(6): 3421–3426.
32.
ShirakiMEndoTSaitoT. Fermentative production of (R)-(-)-3-hydroxybutyrate using 3-hydroxybutyrate dehydrogenase null mutant of Ralstonia eutropha and recombinant Escherichia coli. J Biosci Bioeng2006; 102(6): 529–534.
33.
KataokaMRohaniLPSYamamotoK, et al.Enzymatic production of ethyl (R)-4-chloro-3-hydroxybutanoate: asymmetric reduction of ethyl 4-chloro-3-oxobutanoate by an Escherichia coli transformant expressing the aldehyde reductase gene from yeast. Appl Microbiol Biotechnol1997; 48(6): 699–703.
34.
CalabiaBPTokiwaY. Microbial degradation of poly(D-3-hydroxybutyrate) by a new thermophilic Streptomyces isolate. Biotechnol Lett2004; 26(1): 15–19.
35.
NoyoriROhkumaTKitamuraM, et al.ASYMMETRIC HYDROGENATION OF BETA-KETO CARBOXYLIC ESTERS - A PRACTICAL, PURELY CHEMICAL ACCESS TO BETA-HYDROXY ESTERS IN HIGH ENANTIOMERIC PURITY. J Am Chem Soc1987; 109(19): 5856–5858.
36.
HuangGFHollingsworthRI. An efficient synthesis of (R)-3-hydroxytetradecanoic acid. Tetrahedron-Asymmetry1998; 9(23): 4113–4115.
37.
HuSGJouCHYangMC. Antibacterial and biodegradable properties of polyhydroxyalkanoates grafted with chitosan and chitooligosaccharides via ozone treatment. J Appl Polym Sci2003; 88(12): 2797–2803.
38.
Linlin MaZZLiJunYangXingxing, et alA New Antimicrobial Agent: Poly (3-hydroxybutyric acid) Oligomer. Macromol Biosci2019.
39.
RuthKGrubelnikAHartmannR, et al.Efficient production of (R)-3-hydroxycarboxylic acids by biotechnological conversion of polyhydroxyalkanoates and their purification. Biomacromolecules2007; 8(1): 279–286.
40.
KamraDNJakhmolaRCSinghR. ENSILING OF CATTLE WASTE AND WHEAT STRAW WITH OR WITHOUT GREEN MAIZE. Agric Wastes1984; 9(4): 309–313.
41.
SimoesLCSimoesMVieiraMJ. Adhesion and biofilm formation on polystyrene by drinking water-isolated bacteria. Antonie Van Leeuwenhoek2010; 98(3): 317–329.
42.
LipinskiCALombardoFDominyBW, et al.Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev1997; 23(1–3): 3–25.
43.
ErtlPRohdeBSelzerP. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem2000; 43(20): 3714–3717.
44.
Cotsonas KingAWuL. Macromolecular synthesis and membrane perturbation assays for mechanisms of action studies of antimicrobial agentsc’ Current Protocols in Pharmacology, 2009. Chapter 13:Unit 13A.7-Unit A.7.
45.
ParkSJLeeSYLeeY. Biosynthesis of (R)-3-hydroxyalkanoic acids by metabolically engineered Escherichia coli. Appl Biochem Biotechnol2004; 113: 373–379.
46.
BurtS. Essential oils: their antibacterial properties and potential applications in foods - a review. Int J Food Microbiol2004; 94(3): 223–253.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
