Enhancing the biotransformation of progesterone to the anticancer compound testololactone by Penicillium chrysogenum Ras3009: kinetic modelling and efficiency maximization.

GC-MS analysis Kinetic modelling Pharmaceutical compounds Progesterone Steroids biotransformation Testololactone

Journal

BMC biotechnology
ISSN: 1472-6750
Titre abrégé: BMC Biotechnol
Pays: England
ID NLM: 101088663

Informations de publication

Date de publication:
04 Oct 2024
Historique:
received: 22 07 2024
accepted: 12 09 2024
medline: 5 10 2024
pubmed: 5 10 2024
entrez: 4 10 2024
Statut: epublish

Résumé

Biotransformation of steroid compounds into therapeutic products using microorganisms offers an eco-friendly and economically sustainable approach to the pharmaceutical industry rather than a chemical synthesis way. The biotransformation efficiency of progesterone into the anticancer compound testololactone using Penicillium chrysogenum Ras3009 has been investigated. Besides, maximization of testololactone formation was achieved by studying the kinetic modelling and impact of some fermentation conditions on the biotransformation process. The fungal strain Ras3009 was selected among twelve fungal strains as the most runner for the transformation of 81.18% of progesterone into testololactone. Ras3009 was identified phenotypically and genotypically as Penicillium chrysogenum, its 18 S rRNA nucleotide sequence was deposited in the GenBank database by the accession number OR480104. Studying the impact of fermentation conditions on biotransformation efficiency indicated a positive correlation between substrate concentration and testololactone formation until reaching the maximum velocity v Fungi can be promising biocatalysts for steroid transformation into valuable chemicals and pharmaceutical compounds. The study revealed that the new fungal isolate P. chrysogenum Ras3009 possesses a great catalytic ability to convert progesterone into testololactone. Kinetic modelling analysis and optimization of the fermentation conditions lead to higher transformation efficiency and provide a better understanding of the transformation processes.

Sections du résumé

BACKGROUND BACKGROUND
Biotransformation of steroid compounds into therapeutic products using microorganisms offers an eco-friendly and economically sustainable approach to the pharmaceutical industry rather than a chemical synthesis way. The biotransformation efficiency of progesterone into the anticancer compound testololactone using Penicillium chrysogenum Ras3009 has been investigated. Besides, maximization of testololactone formation was achieved by studying the kinetic modelling and impact of some fermentation conditions on the biotransformation process.
RESULTS RESULTS
The fungal strain Ras3009 was selected among twelve fungal strains as the most runner for the transformation of 81.18% of progesterone into testololactone. Ras3009 was identified phenotypically and genotypically as Penicillium chrysogenum, its 18 S rRNA nucleotide sequence was deposited in the GenBank database by the accession number OR480104. Studying the impact of fermentation conditions on biotransformation efficiency indicated a positive correlation between substrate concentration and testololactone formation until reaching the maximum velocity v
CONCLUSIONS CONCLUSIONS
Fungi can be promising biocatalysts for steroid transformation into valuable chemicals and pharmaceutical compounds. The study revealed that the new fungal isolate P. chrysogenum Ras3009 possesses a great catalytic ability to convert progesterone into testololactone. Kinetic modelling analysis and optimization of the fermentation conditions lead to higher transformation efficiency and provide a better understanding of the transformation processes.

Identifiants

pubmed: 39367307
doi: 10.1186/s12896-024-00896-9
pii: 10.1186/s12896-024-00896-9
doi:

Substances chimiques

Progesterone 4G7DS2Q64Y
Antineoplastic Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

73

Informations de copyright

© 2024. The Author(s).

Références

Mohammad MY, Shakya A, Al-Bakain R, Haroon MH, Choudhary MI. New Monoterpenoid by biotransformation of thymoquinone using aspergillus Niger. Bioorg Chem. 2018;80:212–5. https://doi.org/10.1016/j.bioorg.2018.06.019 .
doi: 10.1016/j.bioorg.2018.06.019 pubmed: 29957489
Al-Dulaimi Q, Mohammad MY, Al-Najdawi M, Al-Hiari YM, Haniffa HM, Choudhary MI. New Bicyclic Lactone by Biotransformation of β-caryophyllene using aspergillus Niger. Lett Org Chem. 2022;19(12):1132–5. https://doi.org/10.2174/1570178619666220615094240 .
doi: 10.2174/1570178619666220615094240
An X, Gao P, Zhao S, Zhu L, You X, Li C, et al. Biotransformation of androst-4-ene-3,17-dione by three fungal species Fusarium solani BH1031, aspergillus awamori MH18 and Mucor circinelloides W12. Nat Prod Res. 2019. https://doi.org/10.1080/14786419.2019.1636238 .
doi: 10.1080/14786419.2019.1636238 pubmed: 31429310
Zoghi M, Gandomkar S, Habibi Z. Biotransformation of progesterone and testosterone enanthate by Circinella muscae. Steroids. 2019;151:108446. https://doi.org/10.1016/j.steroids.2019.108446 .
doi: 10.1016/j.steroids.2019.108446 pubmed: 31302114
Inoue M, Sumii Y, Shibata N. Contribution of organofluorine compounds to pharmaceuticals. ACS Omega. 2020;5(19):10633–40. https://doi.org/10.1021/acsomega.0c00830 .
doi: 10.1021/acsomega.0c00830 pubmed: 32455181 pmcid: 7240833
Brito V, Alves G, Almeida P, Silvestre S. Highlights on steroidal arylidene derivatives as a source of pharmacologically active compounds: a review. Molecules. 2021;26(7):2032. https://doi.org/10.3390/molecules26072032 .
doi: 10.3390/molecules26072032 pubmed: 33918373 pmcid: 8038301
Bruscoli S, Febo M, Riccardi C, Migliorati G. Glucocorticoid therapy in inflammatory bowel disease: mechanisms and clinical practice. Front Immunol. 2021;12:691480. https://doi.org/10.3389/fimmu.2021.691480 .
doi: 10.3389/fimmu.2021.691480 pubmed: 34149734 pmcid: 8209469
Marzbani C, Bhimaraj A. Corticosteroids in immunosuppression. Handb Exp Pharmacol. 2022;272:73–84. https://doi.org/10.1007/164_2021_567 .
doi: 10.1007/164_2021_567 pubmed: 35156139
Kozłowska E, Matera A, Sycz J, Kancelista A, Kostrzewa-Susłow E, Janeczko T. New 6,19-oxidoandrostan derivatives obtained by biotransformation in environmental filamentous fungi cultures. Microb Cell Fact. 2020;19:37. https://doi.org/10.1186/s12934-020-01303-6 .
doi: 10.1186/s12934-020-01303-6 pubmed: 32066453 pmcid: 7026961
Na MS, Tantawy MA, Elmgeed GA. Screening of different drug design tools to predict the mode of action of steroidal derivatives as anti-cancer agents. Steroids 2019;152. https://doi.org/10.1016/j.steroids.2019.108485
Jursic BS, Kumar S, Creech CC, Neumann DM. Novel and efficient synthesis and antifungal evaluation of 2,3-functionalized cholestane and androstane derivatives. Bioorg Med Chem Lett. 2020;20:7372–5. https://doi.org/10.1016/j.bmcl.2010.10.044 .
doi: 10.1016/j.bmcl.2010.10.044
Banday AH, Zargar MI, Ganaie BA. Synthesis and antimicrobial studies of chalconyl pregnenolones. Steroids. 2011;76:1358–62. https://doi.org/10.1016/j.steroids.2011.07.001 .
doi: 10.1016/j.steroids.2011.07.001 pubmed: 21771607
Fernandes P, Cruz A, Angelova B, Pinheiro HM, Cabral JMS. Microbial conversion of steroid compounds: recent developments. Enzyme Microb Technol. 2003;32(6):688–705. https://doi.org/10.1016/S0141-0229(03)00029-2 .
doi: 10.1016/S0141-0229(03)00029-2
Costa S, Tedeschi P, Ferraro L, Beggiato S, Grandini A, Manfredini S, Buzzi R, Sacchetti G, Valacchi G. Biological activity of new bioactive steroids deriving from biotransformation of cortisone. Microb Cell Fact. 2022;21:250. https://doi.org/10.1186/s12934-022-01967-2 .
doi: 10.1186/s12934-022-01967-2 pubmed: 36419154 pmcid: 9685055
Choudhary MI, Mohammad MY, Musharraf SG, Parvez M, Al-Aboudi A, Atta-ur-Rahman. New oxandrolone derivatives by biotransformation using Rhizopus stolonifer. Steroids. 2009;74(13–14):1040–4. https://doi.org/10.1016/j.steroids.2009.08.003 .
doi: 10.1016/j.steroids.2009.08.003 pubmed: 19698730
Al-Aboudi A, Mohammad MY, Musharraf SG, Choudhary MI, Atta-ur-Rahman. Microbial transformation of testosterone by Rhizopus stolonifer and Fusarium lini. Nat Prod Res. 2008;22(17):1498–509. https://doi.org/10.1080/14786410802234528 .
doi: 10.1080/14786410802234528 pubmed: 19023814
Mohammad MY, Musharraf SG, Al-Majid AM, Atta-ur-Rahman, Choudhary MI. Biotransformation of mestanolone and 17-methyl-1-testosterone by Rhizopus stolonifer. Biocatal Biotransfor. 2013;31(4):153–9. https://doi.org/10.3109/10242422.2013.801017 .
doi: 10.3109/10242422.2013.801017
Donova M. Microbial steroid production technologies: current trends and prospects. Microorganisms. 2021;10(1):53. https://doi.org/10.3390/microorganisms10010053 .
doi: 10.3390/microorganisms10010053 pubmed: 35056503 pmcid: 8779116
Murray HC, Peterson H. Oxygenation of steroids by mucorales fungi. US Patent, US2602769 A. 1952.
Chiang YR, Wei ST, Wang PH, Wu PH, Yu CP. Microbial degradation of steroid sex hormones: implications for environmental and ecological studies. Microb Biotechnol. 2020;13(4):926–49. https://doi.org/10.1111/1751-7915.13504 .
doi: 10.1111/1751-7915.13504 pubmed: 31668018
Mohamed SS, El-Hadi AA, Abo-Zied KM. Biotransformation of prednisolone to hydroxy derivatives by Penicillium Aurantiacum. Biocataly Biotransform. 2017;35:215–22. https://doi.org/10.1080/10242422.2017.1316265 .
doi: 10.1080/10242422.2017.1316265
Savinova OS, Solyev PN, Vasina DV, Tyazhelova TV, Fedorova TV, Savinova TS. Biotransformation of progesterone by Aspergillus Nidulans VKPM F-1069 (wild type). Steroids. 2019;149:108421. https://doi.org/10.1016/j.steroids.2019.05.013 .
doi: 10.1016/j.steroids.2019.05.013 pubmed: 31176657
Valko-Rokytovská M, Očenáš P, Salayová A, Kostecká Z. Breast Cancer: targeting of steroid hormones in cancerogenesis and diagnostics. Int J Mol Sci. 2021;22(11):5878. https://doi.org/10.3390/ijms22115878 .
doi: 10.3390/ijms22115878 pubmed: 34070921 pmcid: 8199112
Savic MP, Kuzminac IZ, Nikolic AR. Testolactone: the rise and fall of a drug. Drugs Drug Candidates. 2023;2:69–94. https://doi.org/10.3390/ddc2010005 .
doi: 10.3390/ddc2010005
Visagie CM, Houbraken J, Frisvad JC, Hong SB, Klaassen CH, Perrone G, Seifert KA, Varga J, Yaguchi T, Samson RA. Identification and nomenclature of the genus Penicillium. Stud Mycol. 2014;78:343–71. https://doi.org/10.1016/j.simyco.2014.09.001 .
doi: 10.1016/j.simyco.2014.09.001 pubmed: 25505353 pmcid: 4261876
Rasmey AM, Aboseidah AA, Gaber S, Mahran F. Characterization and optimization of lipase activity by Pseudomonas monteilli 2403-KY120354 isolated from ground beef. Afr J Biotechnol. 2017;6:96–105.
Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol. 2016;33:1870–4.
doi: 10.1093/molbev/msw054 pubmed: 27004904 pmcid: 8210823
Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987;4:406–25.
pubmed: 3447015
Tamura K, Nei M, Kumar S. Prospects for inferring very large phylogenies by using the neighborjoining method. Proc Natl Acad Sci. 2004;101:11030–5.
doi: 10.1073/pnas.0404206101 pubmed: 15258291 pmcid: 491989
Kolatorova L, Vitku J, Suchopar J, Hill M, Parizek A, Progesterone. A steroid with wide range of effects in physiology as well as human medicine. Int J Mol Sci. 2022;23:7989. https://doi.org/10.3390/ijms23147989 .
doi: 10.3390/ijms23147989 pubmed: 35887338 pmcid: 9322133
Lone SH, Bhat KA. Phytosterols as precursors for the synthesis of aromatase inhibitors: Hemisynthesis of testololactone and testolactone. Steroids. 2015;96:164-8. https://doi.org/110.1016/j.steroids.2015.02.011.
Manna PR, Molehin D, Ahmed AU. Dysregulation of aromatase in breast, endometrial, and ovarian cancers: an overview of therapeutic strategies. Prog Mol Biol Transl Sci. 2016;144:487–537. https://doi.org/10.1016/bs.pmbts.2016.10.002 .
doi: 10.1016/bs.pmbts.2016.10.002 pubmed: 27865465
Cuhaci N, Polat SB, Evranos B, Ersoy R, Cakir B. Gynecomastia: clinical evaluation and management. Indian J Endocrinol Metab. 2014;18(2):150–8. https://doi.org/10.4103/2230-8210.129104 .
doi: 10.4103/2230-8210.129104 pubmed: 24741509 pmcid: 3987263
Zhang H, Ren J, Wang Y, Sheng C, Wu Q, Diao A, Zhu D. Effective multi-step functional biotransformations of steroids by a newly isolated Fusarium oxysporum SC1301. Tetrahedron. 2013;69:184–89.
doi: 10.1016/j.tet.2012.10.047
Fürst MJLJ, Gran-Scheuch A, Aalbers FS, Fraaije MW. Baeyer–Villiger monooxygenases: tunable oxidative biocatalysts. ACS Catal. 2019;9:11207–41.
doi: 10.1021/acscatal.9b03396
Mascotti ML, Palazzolo MA, Bisogno FR, Kurina-Sanz M. Biotransformation of dehydro-epi-androsterone by Aspergillus Parasiticus: metabolic evidences of BVMO activity. Steroids. 2016;109:44–9.
doi: 10.1016/j.steroids.2016.03.018 pubmed: 27025973
Gilbert I, White M. Fermentation method for the preparation of testolactone by Fusarium species. US Patent Application. 2006;10:573–636.
Javid M, Nickavar B, Vahidi H, Faramarzi MA. Baeyer-Villiger oxidation of progesterone by aspergillus sojae PTCC 5196. Steroids. 2018;140:52–7.
doi: 10.1016/j.steroids.2018.07.008 pubmed: 30055193
Hunter AC, Carragher NEJ. Flexibility of the endogenous progesterone lactonisation pathway in Aspergillus Tamarii KITA: transformation of a series of cortical steroid analogues. Steroid Biochem Mol Biol. 2003;87:301–8.
doi: 10.1016/j.jsbmb.2003.10.001
Cardoso de Paula SF, Porto ALM. Cascate reactions of progesterone by mycelia and culture broth from marine-derived fungus aspergillus sydowii CBMAI 935. Biocatal Agric Biotechnol. 2020;25:101546.
doi: 10.1016/j.bcab.2020.101546
Bartmańska A, Dmochowska-Gładysz J, Huszcza E. Steroids’ transformations in Penicillium notatum culture. Steroids. 2005;70:193–8.
doi: 10.1016/j.steroids.2004.11.011 pubmed: 15763598
Ko1ek T, Szpineter A, Świzdor A. Studies on Baeyer–Villiger oxidation of steroids: DHEA and pregnenolone d-lactonization pathways in Penicillium Camemberti AM83. Steroids. 2009;74:859–62.
doi: 10.1016/j.steroids.2009.05.007 pubmed: 19481558
Yang B, Wang Y, Chen X, Feng J, Wu Q, Zhu D, Ma Y. Biotransformations of steroids to testololactone by a multifunctional strain Penicillium Simplicissimum WY134-2. Tetrahedron. 2014;70:41–6. https://doi.org/10.1016/j.tet.2013.11.039 .
doi: 10.1016/j.tet.2013.11.039
Robinson PK. Enzymes: principles and biotechnological applications. Essays Biochem. 2015;59:1–41. https://doi.org/10.1042/bse0590001 .
doi: 10.1042/bse0590001 pubmed: 26504249 pmcid: 4692135
Almquist J, Cvijovic M, Hatzimanikatis V, Nielsen J, Jirstrand M. Kinetic models in industrial biotechnology-improving cell factory performance. Metab Eng. 2014;24:38–60. https://doi.org/10.1016/j.ymben.2014.03.007 .
doi: 10.1016/j.ymben.2014.03.007 pubmed: 24747045
Imamoglu E, Sukan FV. Scale-up and kinetic modeling for bioethanol production. Bioresour Technol. 2013;144:311–20. https://doi.org/10.1016/j.biortech.2013.06.118 .
doi: 10.1016/j.biortech.2013.06.118 pubmed: 23886851
Hawary H, Marwa AKM, Rasmey AHM. Kinetic modeling and optimization of ethanol fermentation by the marine yeast Wickerhamomyces Subpelliculosus ZE75. World J Microbiol Biotechnol. 2024;40:155. https://doi.org/10.1007/s11274-024-03942-y .
doi: 10.1007/s11274-024-03942-y pubmed: 38581587 pmcid: 10998816
Li YJ, Zheng YC, Geng Q, Liu F, Zhang ZJ, Xu JH, Yu HL. Secretory expression of cyclohexanone monooxygenase by methylotrophic yeast for efficient omeprazole sulfide bio-oxidation. Bioresour Bioprocess. 2021;8:81. https://doi.org/10.1186/s40643-021-00430- .
doi: 10.1186/s40643-021-00430 pubmed: 38650277 pmcid: 10992682

Auteurs

Marwa M Abdel-Kareem (MM)

Department of Botany and Microbiology, Faculty of Science, Sohag University, Sohag, EG-82524, Egypt.

Abdel-Nasser A Zohri (AA)

Department of Botany and Microbiology, Faculty of Science, Assiut University, Assiut, EG-71516, Egypt.

Abdel-Hamied M Rasmey (AM)

Department of Botany and Microbiology, Faculty of Science, Suez University, P.O.Box: 43221, Suez, Egypt. Abdel-Hamied.rasmey@sci.suezuni.edu.eg.

Heba Hawary (H)

Department of Botany and Microbiology, Faculty of Science, Suez University, P.O.Box: 43221, Suez, Egypt.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs
Humans Male Female Health Knowledge, Attitudes, Practice Middle Aged
Humans Female Alopecia Breast Neoplasms Middle Aged
Saccharomyces cerevisiae Aldehydes Biotransformation Flavoring Agents Lipoxygenase

Classifications MeSH