A type III polyketide synthase cluster in the phylum Planctomycetota is involved in alkylresorcinol biosynthesis.
Chemical mediators
Corynebacterium glutamicum
Hierridin
Planctomycetes
Polyketide-derived compounds
Journal
Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612
Informations de publication
Date de publication:
26 Feb 2024
26 Feb 2024
Historique:
received:
21
11
2023
accepted:
08
02
2024
revised:
29
01
2024
medline:
26
2
2024
pubmed:
26
2
2024
entrez:
26
2
2024
Statut:
epublish
Résumé
Members of the bacterial phylum Planctomycetota have recently emerged as promising and for the most part untapped sources of novel bioactive compounds. The characterization of more than 100 novel species in the last decade stimulated recent bioprospection studies that start to unveil the chemical repertoire of the phylum. In this study, we performed systematic bioinformatic analyses based on the genomes of all 131 described members of the current phylum focusing on the identification of type III polyketide synthase (PKS) genes. Type III PKSs are versatile enzymes involved in the biosynthesis of a wide array of structurally diverse natural products with potent biological activities. We identified 96 putative type III PKS genes of which 58 are encoded in an operon with genes encoding a putative oxidoreductase and a methyltransferase. Sequence similarities on protein level and the genetic organization of the operon point towards a functional link to the structurally related hierridins recently discovered in picocyanobacteria. The heterologous expression of planctomycetal type III PKS genes from strains belonging to different families in an engineered Corynebacterium glutamicum strain led to the biosynthesis of pentadecyl- and heptadecylresorcinols. Phenotypic assays performed with the heterologous producer strains and a constructed type III PKS gene deletion mutant suggest that the natural function of the identified compounds differs from that confirmed in other bacterial alkylresorcinol producers. KEY POINTS: • Planctomycetal type III polyketide synthases synthesize long-chain alkylresorcinols. • Phylogenetic analyses suggest an ecological link to picocyanobacterial hierridins. • Engineered C. glutamicum is suitable for an expression of planctomycete-derived genes.
Identifiants
pubmed: 38407604
doi: 10.1007/s00253-024-13065-x
pii: 10.1007/s00253-024-13065-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
239Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 239748522
Organisme : Deutsche Forschungsgemeinschaft
ID : 239748522
Organisme : HORIZON EUROPE European Research Council
ID : 802736
Organisme : HORIZON EUROPE European Research Council
ID : 802736
Informations de copyright
© 2024. The Author(s).
Références
Anand A, Verma P, Singh Anil K, Kaushik S, Pandey R, Shi C, Kaur H, Chawla M, Elechalawar Chandra K, Kumar D, Yang Y, Bhavesh Neel S, Banerjee R, Dash D, Singh A, Natarajan Vivek T, Ojha Anil K, Aldrich Courtney C, Gokhale Rajesh S (2015) Polyketide quinones are alternate intermediate electron carriers during mycobacterial respiration in oxygen-deficient niches. Mol Cell 60(4):637–650. https://doi.org/10.1016/j.molcel.2015.10.016
doi: 10.1016/j.molcel.2015.10.016
pubmed: 26585386
pmcid: 6051517
Andrés-Lacueva et al., 2009 Andrés‐Lacueva C, Medina‐Remon A, Llorach R, Urpi‐Sarda M, Khan N, Chiva‐Blanch G, Zamora‐Ros R, Rotches‐Ribalta M, Lamuela‐Raventós RM (2009) Phenolic compounds: chemistry and occurrence in fruits and vegetables. In Fruit and vegetable phytochemicals (eds L.A. de la Rosa, E. Alvarez-Parrilla and G.A. González-Aguilar). doi:10.1002/ 9780813809397.ch2
Awakawa T, Fujita N, Hayakawa M, Ohnishi Y, Horinouchi S (2011) Characterization of the biosynthesis gene cluster for alkyl-O-dihydrogeranyl-methoxyhydroquinones in Actinoplanes missouriensis. ChemBioChem 12(3):439–448. https://doi.org/10.1002/cbic.201000628
doi: 10.1002/cbic.201000628
pubmed: 21264995
Bertani G (1951) Studies on lysogenesis I: the mode of phage liberation by lysogenic Escherichia coli. J Bacteriol 62(3):293
doi: 10.1128/jb.62.3.293-300.1951
pubmed: 14888646
pmcid: 386127
Bhan N, Li L, Cai C, Xu P, Linhardt RJ, Koffas MAG (2015) Enzymatic formation of a resorcylic acid by creating a structure-guided single-point mutation in stilbene synthase. Protein Sci 24(2):167–173. https://doi.org/10.1002/pro.2600
doi: 10.1002/pro.2600
pubmed: 25402946
Blin K, Shaw S, Kloosterman AM, Charlop-Powers Z, van Wezel GP, Medema Marnix H, Weber T (2021) antiSMASH 6.0: improving cluster detection and comparison capabilities. Nucleic Acids Res 49(W1):W29–W35. https://doi.org/10.1093/nar/gkab335
doi: 10.1093/nar/gkab335
pubmed: 33978755
pmcid: 8262755
Brandão P, Moreira J, Almeida J, Nazareth N, Sampaio-Dias IE, Vasconcelos V, Martins R, Leão P, Pinto M, Saraíva L, Cidade H (2020) Norhierridin B, a new hierridin B-based hydroquinone with improved antiproliferative activity. Molecules 25(7):1578
doi: 10.3390/molecules25071578
pubmed: 32235535
pmcid: 7181126
Costa M, Sampaio-Dias IE, Castelo-Branco R, Scharfenstein H, Rezende de Castro R, Silva A, Schneider MPC, Araújo MJ, Martins R, Domingues VF, Nogueira F, Camões V, Vasconcelos VM, Leão PN (2019) Structure of hierridin C, synthesis of hierridins B and C, and evidence for prevalent alkylresorcinol biosynthesis in picocyanobacteria. J Nat Prod 82(2):393–402. https://doi.org/10.1021/acs.jnatprod.8b01038
doi: 10.1021/acs.jnatprod.8b01038
pubmed: 30715888
Dedysh SN, Kulichevskaya IS, Beletsky AV, Ivanova AA, Rijpstra WIC, Damsté JSS, Mardanov AV, Ravin NV (2020) Lacipirellula parvula gen. nov., sp. nov., representing a lineage of planctomycetes widespread in low-oxygen habitats, description of the family Lacipirellulaceae fam. nov. and proposal of the orders Pirellulales ord. nov., Gemmatales ord. nov. and Isosphaerales ord. nov. Syst Appl Microbiol 43(1):126050. https://doi.org/10.1016/j.syapm.2019.126050
doi: 10.1016/j.syapm.2019.126050
pubmed: 31882205
pmcid: 6995999
Donner J, Reck M, Bunk B, Jarek M, App CB, Meier-Kolthoff JP, Overmann J, Müller R, Kirschning A, Wagner-Döbler I (2017) The biofilm inhibitor carolacton enters gram-negative cells: studies using a TolC-deficient strain of Escherichia coli. mSphere 2(5). https://doi.org/10.1128/mSphereDirect.00375-17
Eggeling L, Bott M (2005) Handbook of Corynebacterium glutamicum. CRC Press, Boca Raton, FL, USA
doi: 10.1201/9781420039696
Eggeling L, Bott M (2015) A giant market and a powerful metabolism: L-lysine provided by Corynebacterium glutamicum. Appl Microbiol Biotechnol 99(8):3387–3394. https://doi.org/10.1007/s00253-015-6508-2
doi: 10.1007/s00253-015-6508-2
pubmed: 25761623
Funabashi M, Funa N, Horinouchi S (2008) Phenolic lipids synthesized by type III polyketide synthase confer penicillin resistance on Streptomyces griseus*. J Biol Chem 283(20):13983–13991. https://doi.org/10.1074/jbc.M710461200
doi: 10.1074/jbc.M710461200
pubmed: 18364359
Gande R, Dover LG, Krumbach K, Besra GS, Sahm H, Oikawa T, Eggeling L (2007) The two carboxylases of Corynebacterium glutamicum essential for fatty acid and mycolic acid synthesis. J Bacteriol 189(14):5257–5264
doi: 10.1128/JB.00254-07
pubmed: 17483212
pmcid: 1951862
Gonzalez AG, Bermejo Barrera J, Rodriguez Perez ME (1992) Synthesis of hierridin, a phenol from the lichen Ramalina hierrensis. Phytochemistry 31(4):1436–1439. https://doi.org/10.1016/0031-9422(92)80314-5
Hayashi T, Kitamura Y, Funa N, Ohnishi Y, Horinouchi S (2011) Fatty acyl-AMP ligase involvement in the production of alkylresorcylic acid by a Myxococcus xanthus type III polyketide synthase. ChemBioChem 12(14):2166–2176. https://doi.org/10.1002/cbic.201100344
doi: 10.1002/cbic.201100344
pubmed: 21815236
Hug LA, Baker BJ, Anantharaman K, Brown CT, Probst AJ, Castelle CJ, Butterfield CN, Hernsdorf AW, Amano Y, Ise K, Suzuki Y, Dudek N, Relman DA, Finstad KM, Amundson R, Thomas BC, Banfield JF (2016) A new view of the tree of life. Nat Microbiol 1(5):16048. https://doi.org/10.1038/nmicrobiol.2016.48
doi: 10.1038/nmicrobiol.2016.48
pubmed: 27572647
Ivanova A, Dedysh S (2012) Abundance, diversity, and depth distribution of Planctomycetes in acidic northern wetlands. Front Microbiol 3(5). https://doi.org/10.3389/fmicb.2012.00005
Kallscheuer N, Jogler C (2021) The bacterial phylum Planctomycetes as novel source for bioactive small molecules. Biotechnol Adv 53:107818. https://doi.org/10.1016/j.biotechadv.2021.107818
doi: 10.1016/j.biotechadv.2021.107818
pubmed: 34537319
Kallscheuer N, Marienhagen J (2018) Corynebacterium glutamicum as platform for the production of hydroxybenzoic acids. Microbial Cell Fact 17(1):70. https://doi.org/10.1186/s12934-018-0923-x
doi: 10.1186/s12934-018-0923-x
Kallscheuer N, Vogt M, Stenzel A, Gätgens J, Bott M, Marienhagen J (2016) Construction of a Corynebacterium glutamicum platform strain for the production of stilbenes and (2S)-flavanones. Metab Eng 38:47–55
doi: 10.1016/j.ymben.2016.06.003
pubmed: 27288926
Kallscheuer N, Vogt M, Bott M, Marienhagen J (2017) Functional expression of plant-derived O-methyltransferase, flavanone 3-hydroxylase, and flavonol synthase in Corynebacterium glutamicum for production of pterostilbene, kaempferol, and quercetin. J Biotechnol 258:190–196. https://doi.org/10.1016/j.jbiotec.2017.01.006
doi: 10.1016/j.jbiotec.2017.01.006
pubmed: 28143765
Kallscheuer N, Kage H, Milke L, Nett M, Marienhagen J (2019a) Microbial synthesis of the type I polyketide 6-methylsalicylate with Corynebacterium glutamicum. Appl Microbiol Biotechnol 103(23):9619–9631. https://doi.org/10.1007/s00253-019-10121-9
doi: 10.1007/s00253-019-10121-9
pubmed: 31686146
Kallscheuer N, Moreira C, Airs R, Llewellyn CA, Wiegand S, Jogler C, Lage OM (2019b) Pink- and orange-pigmented Planctomycetes produce saproxanthin-type carotenoids including a rare C
doi: 10.1111/1758-2229.12796
pubmed: 31600855
Kallscheuer N, Jeske O, Sandargo B, Boedeker C, Wiegand S, Bartling P, Jogler M, Rohde M, Petersen J, Medema MH, Surup F, Jogler C (2020) The planctomycete Stieleria maiorica Mal15
doi: 10.1038/s42003-020-0993-2
pubmed: 32533057
pmcid: 7293339
Kallscheuer N, Rast P, Jogler M, Wiegand S, Kohn T, Boedeker C, Jeske O, Heuer A, Quast C, Glöckner FO, Rohde M, Jogler C (2021) Analysis of bacterial communities in a municipal duck pond during a phytoplankton bloom and isolation of Anatilimnocola aggregata gen. nov., sp. nov., Lacipirellula limnantheis sp. nov. and Urbifossiella limnaea gen. nov., sp. nov. belonging to the phylum Planctomycetes. Environ Microbiol 23(3):1379–1396. https://doi.org/10.1111/1462-2920.15341
doi: 10.1111/1462-2920.15341
pubmed: 33331109
Keilhauer C, Eggeling L, Sahm H (1993) Isoleucine synthesis in Corynebacterium glutamicum: molecular analysis of the ilvB-ilvN-ilvC operon. J Bacteriol 175(17):5595–5603
doi: 10.1128/jb.175.17.5595-5603.1993
pubmed: 8366043
pmcid: 206616
Kogure T, Inui M (2018) Recent advances in metabolic engineering of Corynebacterium glutamicum for bioproduction of value-added aromatic chemicals and natural products. Appl Microbiol Biotechnol 102(20):8685–8705. https://doi.org/10.1007/s00253-018-9289-6
doi: 10.1007/s00253-018-9289-6
pubmed: 30109397
Kortmann M, Kuhl V, Klaffl S, Bott M (2015) A chromosomally encoded T7 RNA polymerase-dependent gene expression system for Corynebacterium glutamicum: construction and comparative evaluation at the single-cell level. Microbial Biotechnol 8(2):253–265
doi: 10.1111/1751-7915.12236
Kulichevskaya IS, Ivanova AA, Baulina OI, Rijpstra WIC, Sinninghe Damsté JS, Dedysh SN (2017) Fimbriiglobus ruber gen. nov., sp. nov., a Gemmata-like planctomycete from Sphagnum peat bog and the proposal of Gemmataceae fam. nov. Int J Syst Evol Microbiol 67(2):218–224. https://doi.org/10.1099/ijsem.0.001598
doi: 10.1099/ijsem.0.001598
pubmed: 27902209
Lage O, Bondoso J (2012) Bringing Planctomycetes into pure culture. Front Microbiol 3:405. https://doi.org/10.3389/fmicb.2012.00405
doi: 10.3389/fmicb.2012.00405
pubmed: 23335915
pmcid: 3538630
Lage OM, Bondoso J (2014) Planctomycetes and macroalgae, a striking association. Front Microbiol 5:267. https://doi.org/10.3389/fmicb.2014.00267
doi: 10.3389/fmicb.2014.00267
pubmed: 24917860
pmcid: 4042473
Leão PN, Costa M, Ramos V, Pereira AR, Fernandes VC, Domingues VF, Gerwick WH, Vasconcelos VM, Martins R (2013) Antitumor activity of hierridin B, a cyanobacterial secondary metabolite found in both filamentous and unicellular marine strains. PLoS ONE 8(7):e69562. https://doi.org/10.1371/journal.pone.0069562
doi: 10.1371/journal.pone.0069562
pubmed: 23922738
pmcid: 3726634
Letunic I, Bork P (2021) Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 49(W1):W293–W296. https://doi.org/10.1093/nar/gkab301
doi: 10.1093/nar/gkab301
pubmed: 33885785
pmcid: 8265157
Lim CG, Fowler ZL, Hueller T, Schaffer S, Koffas MAG (2011) High-yield resveratrol production in engineered Escherichia coli. Appl Environ Microbiol 77(10):3451–3460. https://doi.org/10.1128/AEM.02186-10
doi: 10.1128/AEM.02186-10
pubmed: 21441338
pmcid: 3126431
Liu H-W, Begley T (2020) Comprehensive natural products III. Elsevier, Amsterdam, Netherlands
Martins TP, Rouger C, Glasser NR, Freitas S, de Fraissinette NB, Balskus EP, Tasdemir D, Leão PN (2019) Chemistry, bioactivity and biosynthesis of cyanobacterial alkylresorcinols. Nat Prod Rep 36(10):1437–1461
doi: 10.1039/C8NP00080H
pubmed: 30702733
pmcid: 6836626
Medema MH, Cimermancic P, Sali A, Takano E, Fischbach MA (2014) A systematic computational analysis of biosynthetic gene cluster evolution: lessons for engineering biosynthesis. PLoS Comp Biol 10(12):e1004016. https://doi.org/10.1371/journal.pcbi.1004016
doi: 10.1371/journal.pcbi.1004016
Meslet-Cladière L, Delage L, Leroux CJ-J, Goulitquer S, Leblanc C, Creis E, Gall EA, Stiger-Pouvreau V, Czjzek M, Potin P (2013) Structure/function analysis of a type III polyketide synthase in the brown alga Ectocarpus siliculosus reveals a biochemical pathway in phlorotannin monomer biosynthesis. Plant Cell 25(8):3089–3103. https://doi.org/10.1105/tpc.113.111336
doi: 10.1105/tpc.113.111336
pubmed: 23983220
pmcid: 3784601
Milke L, Marienhagen J (2020) Engineering intracellular malonyl-CoA availability in microbial hosts and its impact on polyketide and fatty acid synthesis. Appl Microbiol Biotechnol 104(14):6057–6065. https://doi.org/10.1007/s00253-020-10643-7
doi: 10.1007/s00253-020-10643-7
pubmed: 32385515
pmcid: 7316851
Milke L, Aschenbrenner J, Marienhagen J, Kallscheuer N (2018) Production of plant-derived polyphenols in microorganisms: current state and perspectives. Appl Microbiol Biotechnol 102(4):1575–1585. https://doi.org/10.1007/s00253-018-8747-5
doi: 10.1007/s00253-018-8747-5
pubmed: 29340710
Milke L, Kallscheuer N, Kappelmann J, Marienhagen J (2019) Tailoring Corynebacterium glutamicum towards increased malonyl-CoA availability for efficient synthesis of the plant pentaketide noreugenin. Microbial Cell Fact 18(1):71. https://doi.org/10.1186/s12934-019-1117-x
doi: 10.1186/s12934-019-1117-x
Milke L, Mutz M, Marienhagen J (2020) Synthesis of the character impact compound raspberry ketone and additional flavoring phenylbutanoids of biotechnological interest with Corynebacterium glutamicum. Microbial Cell Fact 19(1):92. https://doi.org/10.1186/s12934-020-01351-y
doi: 10.1186/s12934-020-01351-y
Nivina A, Yuet KP, Hsu J, Khosla C (2019) Evolution and diversity of assembly-line polyketide synthases. Chem Rev 119(24):12524–12547. https://doi.org/10.1021/acs.chemrev.9b00525
doi: 10.1021/acs.chemrev.9b00525
pubmed: 31838842
pmcid: 6935866
Overmann J, Abt B, Sikorski J (2017) Present and future of culturing bacteria. Annu Rev Microbiol 71(1):711–730. https://doi.org/10.1146/annurev-micro-090816-093449
doi: 10.1146/annurev-micro-090816-093449
pubmed: 28731846
Paczia N, Nilgen A, Lehmann T, Gätgens J, Wiechert W, Noack S (2012) Extensive exometabolome analysis reveals extended overflow metabolism in various microorganisms. Microbial Cell Fact 11(1):1–14
doi: 10.1186/1475-2859-11-122
Pandith SA, Ramazan S, Khan MI, Reshi ZA, Shah MA (2019) Chalcone synthases (CHSs): the symbolic type III polyketide synthases. Planta 251(1):15. https://doi.org/10.1007/s00425-019-03307-y
doi: 10.1007/s00425-019-03307-y
pubmed: 31776718
Panter F, Garcia R, Thewes A, Zaburannyi N, Bunk B, Overmann J, Gutierrez MV, Krug D, Müller R (2019) Production of a dibrominated aromatic secondary metabolite by a planctomycete implies complex interaction with a macroalgal host. ACS Chem Biol 14(12):2713–2719. https://doi.org/10.1021/acschembio.9b00641
doi: 10.1021/acschembio.9b00641
pubmed: 31644258
Papendorf O, König GM, Wright AD (1998) Hierridin B and 2,4-dimethoxy-6-heptadecyl-phenol, secondary metabolites from the cyanobacterium Phormidium ectocarpi with antiplasmodial activity. Phytochemistry 49(8):2383–2386. https://doi.org/10.1016/S0031-9422(98)00440-3
doi: 10.1016/S0031-9422(98)00440-3
pubmed: 9887530
Parage C, Tavares R, Réty S, Baltenweck-Guyot R, Poutaraud A, Renault L, Heintz D, Lugan R, Marais GAB, Aubourg S, Hugueney P (2012) Structural, functional, and evolutionary analysis of the unusually large stilbene synthase gene family in grapevine. Plant Physiol 160(3):1407–1419. https://doi.org/10.1104/pp.112.202705
doi: 10.1104/pp.112.202705
pubmed: 22961129
pmcid: 3490603
Price MN, Dehal PS, Arkin AP (2010) FastTree 2 – approximately maximum-likelihood trees for large alignments. PLoS ONE 5(3):e9490. https://doi.org/10.1371/journal.pone.0009490
doi: 10.1371/journal.pone.0009490
pubmed: 20224823
pmcid: 2835736
Rivas-Marin E, Wiegand S, Kallscheuer N, Jogler M, Peeters SH, Heuer A, Jetten MSM, Boedeker C, Rohde M, Devos DP, Jogler C (2020) Thalassoglobus polymorphus sp. nov., a novel Planctomycete isolated close to a public beach of Mallorca Island. Antonie Van Leeuwenhoek 113(12):1915–1926. https://doi.org/10.1007/s10482-020-01437-y
doi: 10.1007/s10482-020-01437-y
pubmed: 32583191
pmcid: 7716918
Rozmer Z, Perjési P (2016) Naturally occurring chalcones and their biological activities. Phytochem Rev 15(1):87–120. https://doi.org/10.1007/s11101-014-9387-8
doi: 10.1007/s11101-014-9387-8
Sambrook J, Russell D (2001) Molecular cloning, vol. 1–3. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
Sandargo B, Jeske O, Boedeker C, Wiegand S, Wennrich J-P, Kallscheuer N, Jogler M, Rohde M, Jogler C, Surup F (2020) Stieleriacines, N-acyl dehydrotyrosines from the marine Planctomycete Stieleria neptunia sp. nov. Front Microbiol 11:1408. https://doi.org/10.3389/fmicb.2020.01408
doi: 10.3389/fmicb.2020.01408
pubmed: 32765432
pmcid: 7378531
Santana-Molina C, Henriques V, Hornero-Méndez D, Devos DP, Rivas-Marin E (2022) The squalene route to C
doi: 10.1073/pnas.2210081119
pubmed: 36534808
pmcid: 9907078
Thompson JD, Gibson TJ, Higgins DG (2003) Multiple sequence alignment using ClustalW and ClustalX. Current Protocols in Bioinformatics 2.3.1–2.3.22 doi: https://doi.org/10.1002/0471250953.bi0203s00
Vitorino IR, Lage OM (2022) The Planctomycetia: an overview of the currently largest class within the phylum Planctomycetes. Antonie Van Leeuwenhoek 115(2):169–201. https://doi.org/10.1007/s10482-021-01699-0
doi: 10.1007/s10482-021-01699-0
pubmed: 35037113
Wiegand S, Jogler M, Jogler C (2018) On the maverick Planctomycetes. FEMS Microbiol Rev 42(6):739–760. https://doi.org/10.1093/femsre/fuy029
doi: 10.1093/femsre/fuy029
pubmed: 30052954
Wiegand S, Jogler M, Boedeker C, Pinto D, Vollmers J, Rivas-Marín E, Kohn T, Peeters SH, Heuer A, Rast P, Oberbeckmann S, Bunk B, Jeske O, Meyerdierks A, Storesund JE, Kallscheuer N, Lücker S, Lage OM, Pohl T, Merkel BJ, Hornburger P, Müller R-W, Brümmer F, Labrenz M, Spormann AM, Op den Camp HJM, Overmann J, Amann R, Jetten MSM, Mascher T, Medema MH, Devos DP, Kaster A-K, Øvreås L, Rohde M, Galperin MY, Jogler C (2020) Cultivation and functional characterization of 79 planctomycetes uncovers their unique biology. Nat Microbiol 5(1):126–140. https://doi.org/10.1038/s41564-019-0588-1
doi: 10.1038/s41564-019-0588-1
pubmed: 31740763
Wolf S, Becker J, Tsuge Y, Kawaguchi H, Kondo A, Marienhagen J, Bott M, Wendisch Volker F, Wittmann C (2021) Advances in metabolic engineering of Corynebacterium glutamicum to produce high-value active ingredients for food, feed, human health, and well-being. Essays Biochem 65(2):197–212. https://doi.org/10.1042/ebc20200134
doi: 10.1042/ebc20200134
pubmed: 34096577
pmcid: 8313993
Zabolotneva AA, Shatova OP, Sadova AA, Shestopalov AV, Roumiantsev SA (2022) An overview of alkylresorcinols biological properties and effects. J Nutr Metab 2022:4667607. https://doi.org/10.1155/2022/4667607
doi: 10.1155/2022/4667607
pubmed: 35036005
pmcid: 8754669