Abstract
The goals of this study were to increase the production of antroquinonol (AQ) and to elucidate the response mechanism of the cell membrane during the in situ extractive fermentation (ISEF) of Antrodia camphorata S-29. Through ISEF, the concentration of AQ reached a maximum of 146.1 ± 2.8 mg/L, which was approximately (7.4 ± 0.1)-fold that of the control (coenzyme Q0-induced fermentation). Transcriptome sequencing showed that four genes (FAD2, fabG, SCD, and FAS1) related to fatty acid biosynthesis were upregulated. FAD2 and SCD may regulate the increase in oleic acid (C18:1) and linoleic acid (C18:2) in the cell membrane of A. camphorata S-29, resulting in an increase in cell membrane permeability. AQ was successfully transferred to the n-tetradecane phase through the cell membrane, reducing product feedback inhibition and improving the production of AQ from A. camphorata S-29.
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References
Chang TT, Chou WN (1995) Antrodia cinnamomea sp. nov. on Cinnamomum kanehirai in Taiwan. Mycol Res 99:756–758
Li HX, Lu ZM, Geng Y, Gong JS, Zhang XJ, Shi JS, Xu ZH, Ma YH (2015) Efficient production of bioactive metabolites from Antrodia camphorat ATCC 200183 by asexual reproduction-based repeated batch fermentation. Bioresour Technol 194:334–343
Geethangili M, Tzeng YM (2009) Review of pharmacological effects of Antrodia camphorata and its bioactive compounds. Evid-based Compl Alt 108:1–15
Hu YD, Zhang BB, Xu GR, Liao XR, Cheung PCK (2016) A mechanistic study on the biosynthetic regulation of bioactive metabolite Antroquinonol from edible and medicinal mushroom Antrodia camphorata. J Funct Foods 25:70–79
Chang WH, Chen MC, Cheng IH (2015) Antroquinonol lowers brain amyloid-β levels and improves spatial learning and memory in a transgenic mouse model of Alzheimer’s disease. Sci Rep-UK 5:1–12
Ho CL, Wang JL, Lee CC, Cheng HY, Wen WC, Cheng HHY, Chen MCM (2014) Antroquinonol blocks Ras and Rho signaling via the inhibition of protein isoprenyltransferase activity in cancer cells. Biomed Pharmacother 68:1007–1014
Yu CC, Chiang PC, Lu PH, Kuo MT, Wen WC, Chen P, Guh JH (2012) Antroquinonol, a natural ubiquinone derivative, induces a cross talk between apoptosis, autophagy and senescence in human pancreatic carcinoma cells. J Nutr Biochem 23:900–907
Lee YC, Ho CL, Kao WY, Chen YM (2015) A phase I multicenter study of antroquinonol in patients with metastatic non-small-cell lung cancer who have received at least two prior systemic treatment regimens, including one platinum-based chemotherapy regimen. Mol Clin Oncol 3:1375–1380
Villaume MT, Sella E, Saul G, Borzilleri RM, Fargnoli J, Johnston KA, Zhang H, Fereshteh MP, Dhar TGM, Baran PS (2015) Antroquinonol a: scalable synthesis and preclinical biology of a phase 2 drug candidate. ACS Cent Sci 2:27–31
Brink LES, Tramper J (1985) Optimization of organic solvent in multiphase biocatalysis. Biotechnol Bioeng 27:1258–1269
Nicolaou SA, Gaida SM, Papoutsakis ET (2010) A comparative view of metabolite and substrate stress and tolerance in microbial bioprocessing: from biofuels and chemicals, to biocatalysis and bioremediation. Metab Eng 12:307–331
Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26(1):139–140
Xie C, Mao X, Huang J, Ding Y, Wu J, Dong S, Kong L, Gao G, Li CY, Wei L (2011) KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Res 39:W316–322
Wang YF, Zhang SX, Liu HQ, Zhang L, Yi CF, Li H (2015) Changes and roles of membrane compositions in the adaptation of Saccharomyces cerevisiae to ethanol. J Basic Microb 55:1417–1426
Zhang B, Dong CJ, Shang QM, Han YZ, Li P (2013) New insights into membrane permeabilization of fungal hyphae by the lipopeptide antibiotic bacillomycin L. BBA Biomembr 1828:2230–2237
Clarke JM, Gillings MR, Altavilla N, Beattie AJ (2001) Potential problems with fluorescein diacetate assays of cell viability when testing natural products for antimicrobial activity. J Microbiol Meth 46:261–267
Leon R, Fernandes P, Pinheiro HM, Cabral JMS (1998) Whole-cell biocatalysis in organic media. Enzyme Microb Tech 23:483–500
Wang Z, Dai Z (2010) Extractive microbial fermentation in cloud point system. Enzyme Microb Tech 46:407–418
Liu XF, Xia YJ, Zhang Y, Yi ZW, Meng P, Wang GQ, Ai LZ (2019) Enhancement of antroquinonol and antrodin C productions via in situ extractive fermentation of Antrodia camphorata S-29. Appl Microbiol Biot. https://doi.org/10.1007/s00253-019-10034-7
Evans PJ, Wang HY (1990) Effects of extractive fermentation on butyric acid production by Clostridium acetobutylicum. Appl Microbiol Biotechnol 32:393–397
Chou KCC, Yang SH, Wu HL, Lin PY, Chang TL, Sheu F, Chen KH, Chiang BH (2017) Biosynthesis of antroquinonol and 4-acetylantroquinonol B via polyketide pathway using orsellinic acid as a ring precursor in Antrodia cinnamomea. J Agric Food Chem 65:74–86
Lu ZM, Tao WY, Xu HY, Lim J, Zhang XM, Wang LP, Chen JH, Xu ZH (2011) Analysis of volatile compounds of A. camphorata in submerged culture using headspace solid-phase microextraction. Food Chem 127:662–668
Chiang CC, Huang TN, Lin YW, Chen KS, Chiang BH (2013) Enhancement of 4-acetylantroquinonol B production by supplementation of its precursor during submerged fermentation of Antrodia cinnamomea. J Agr Food Chem 61:9160–9165
Xia YJ, Chen Y, Liu XF, Zhou X, Wang ZC, Wang GQ, Xiong ZQ, Ai LZ (2018) Enhancement of antroquinonol production during batch fermentation using pH control coupled with an oxygen vector. J Sci Food Agric 91:2463–2470
Zhang H, Xia YJ, Wang YL, Zhang BB, Xu GR (2013) Coupling use of surfactant and in situ extractant for enhanced production of Antrodin C by submerged fermentation of Antrodia camphorata. Biochem Eng J 79:194–199
Xia YJ, Zhou X, Wang GQ, Zhang BB, Xu GR, Ai LZ (2017) Induction of AQ production by addition of dissolved oxygen in the fermentation of A. camphorata S-29. J Sci Food Agric 97:595–599
Rise P, Ghezzi S, Priori I, Galli C (2005) Differential modulation by simvastatin of the metabolic pathways in the n-9, n-6 and n-3 fatty acid series, in human monocytic and hepatocytic cell lines. Biochem Pharmacol 69:1095–1100
Fernández AI, Óvilo C, Barragán C, Rodríguez MC, Silió L, Folch JM, Fernández A (2017) Validating porcine SCD haplotype effects on fatty acid desaturation and fat deposition in different genetic backgrounds. Livest Sci 205:98–105
Tezaki S, Iwama R, Kobayashi S, Shiwa Y, Yoshikawa H, Ohta A, Horiuchi H, Fukuda R (2017) D12-fatty acid desaturase is involved in growth at low temperature in yeast Yarrowia lipolytica. Biochem Biophys Res Commun 488:165–170
Weber FJ, de Bont JA (1996) Adaptation mechanisms of microorganisms to the toxic effects of organic solvents on membranes. BBA Rev Biomembr 1286:225–245
Ding J, Huang X, Zhang L, Zhao N, Yang D, Zhang K (2009) Tolerance and stress response to ethanol in the yeast Saccharomyces cerevisiae. Appl Microbiol Biotechnol 85:253–263
Han YZ, Zhao JJ, Zhang B, Shen Q, Shang QM, Li PG (2018) Effect of a novel antifungal peptide P852 on cell morphology and membrane permeability of Fusarium oxysporum. BBA Biomembr. https://doi.org/10.1016/j.bbamem.2018.10.018
Gao J, Kim JS, Terziev N, Cuccui I, Daniel G (2017) Effect of thermal modification on the durability and decay patterns of hardwoods and softwoods exposed to soft rot fungi. Int Biodeter Biodegr 127:35–45
Rotman B, Papermaster BW (1966) Membranne properties of living mammalian cells as studied by enzymatic hydrolysis of fluoresceinic esters. Proc Natl Acad Sci 55:134–141
Chrzanowski TH, Crotty RD, Hubbard JG, Welch RP (1984) Applicability of the fluorescein diacetate method of detecting active bacteria in freshwater. Microb Ecol 10:179–185
Li GC, Hahn GM (1978) Ethanol-induced tolerance to heat and to Adriamycin. Nature 274:699–701
Mcelhaney RN, Gier JD, Neutkok ECMVD (1970) The effect of alterations in fatty acid composition and cholesterol content on the nonelectrolyte permeability of Acholeplasma laidlawii B cells and derived liposomes. BBA Biomembr 219(1):245–247
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This work was supported by the National Natural Science Foundation of China (Grant No. 31871757), Shanghai Engineering Research Center of Food Microbiology (Grant No. 19 DZ2281100), and the Hujiang Foundation of China (Grant No. D15012).
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Liu, XF., Xia, YJ., Lai, P.FH. et al. An increase in cell membrane permeability in the in situ extractive fermentation improves the production of antroquinonol from Antrodia camphorata S-29. J Ind Microbiol Biotechnol 47, 197–207 (2020). https://doi.org/10.1007/s10295-020-02258-8
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DOI: https://doi.org/10.1007/s10295-020-02258-8