{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:36:17Z","timestamp":1786977377265,"version":"build-2736575974"},"reference-count":145,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T00:00:00Z","timestamp":1665187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["5\/3\/8\/13\/2019\u2010ITR"],"award-info":[{"award-number":["5\/3\/8\/13\/2019\u2010ITR"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Microorganisms are known to produce pharmaceutically important secondary metabolites that are used as drug moieties in the treatment of various disorders. Discovery of one such class of drugs called immunosuppressants led the way for new and improved treatment regimens for the cases of organ rejections as well as for autoimmune diseases. Uncovering the role of these secondary metabolites as immunomodulators had increased their demand in the global drug market. However, this was soon overshadowed by the low amount of product obtained after fermentation and tedious downstream processing for the recovery of product. Hence, continuous efforts are being made to enhance their production by unveiling the basic biosynthetic pathways involved in their synthesis. From unearthing these immunosuppressants to their rapid development towards commercialization, these drugs have gained a significant place in the world market. Hence, the present review is focused on the progress and challenges in the production and downstream processing of different immunosuppressants (tacrolimus, cyclosporine, rapamycin, and mycophenolic acid). This is the first review report on how the market demand of immunosuppressants could be fulfilled by exploring biofoundry approaches to achieve the goal.<\/jats:p>","DOI":"10.1002\/bit.28231","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T02:20:21Z","timestamp":1663294821000},"page":"3339-3369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Progress and challenges in the biofoundry of immunosuppressants: From process to practice"],"prefix":"10.1002","volume":"119","author":[{"given":"Ananta","family":"Ganjoo","sequence":"first","affiliation":[{"name":"Fermentation and Microbial Biotechnology Division CSIR\u2010Indian Institute of Integrative Medicine Jammu Jammu &amp; Kashmir India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitika","family":"Sharma","sequence":"additional","affiliation":[{"name":"Fermentation and Microbial Biotechnology Division CSIR\u2010Indian Institute of Integrative Medicine Jammu Jammu &amp; Kashmir India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haseena","family":"Shafeeq","sequence":"additional","affiliation":[{"name":"Fermentation and Microbial Biotechnology Division CSIR\u2010Indian Institute of Integrative Medicine Jammu Jammu &amp; Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nargis A.","family":"Bhat","sequence":"additional","affiliation":[{"name":"Fermentation and Microbial Biotechnology Division CSIR\u2010Indian Institute of Integrative Medicine Jammu Jammu &amp; Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashyap K.","family":"Dubey","sequence":"additional","affiliation":[{"name":"Laboratory of Bioprocess Engineering Jawaharlal Nehru University New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9784-4135","authenticated-orcid":false,"given":"Vikash","family":"Babu","sequence":"additional","affiliation":[{"name":"Fermentation and Microbial Biotechnology Division CSIR\u2010Indian Institute of Integrative Medicine Jammu Jammu &amp; Kashmir India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01026092"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1656(90)90132-u"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-008-0931-z"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2008.11.005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-3109(00)00188-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000186390.10150.66"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-019-03204-w"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/0250-474X.107082"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3329\/bjp.v7i1.10084"},{"issue":"21","key":"e_1_2_10_11_1","first-page":"72","article-title":"Increased yield of cyclosporin A obtained using physical and chemical mutagenesis and medium optimization","volume":"10","author":"Babu P.","year":"2022","journal-title":"International Journal of Research in Engineering and Science (IJRES)"},{"key":"e_1_2_10_12_1","unstructured":"Bakhtiari M. R. Moazami N. Falahpour M. Mirdamadi S. Tabatabaei M. NOUROUZIAN D. &Mohseni F.(2003).Production and purification of cyclosporin A from fermentation broth ofTolypocladium inflatum.https:\/\/www.sid.ir\/en\/journal\/ViewPaper.aspx?id=97752"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e328364db84"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-020-11064-2"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-013-5362-3"},{"issue":"4","key":"e_1_2_10_16_1","first-page":"525","article-title":"Optimization of media composition for the production of cyclosporin a by Tolypocladium species","volume":"123","author":"Balaraman K.","year":"2006","journal-title":"The Indian Journal of Medical Research"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20263"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007050050629"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7613.103235"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-009-1918-7"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986710791163920"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47212-2"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","unstructured":"Colombo D. &Pietro A. D.(2012). Systemic cyclosporin in the treatment of psoriasis. In J. Soung & B. Koo (Eds.) Psoriasis.https:\/\/doi.org\/10.5772\/27484","DOI":"10.5772\/27484"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-021-01102-5"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00928431"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-017-2260-3"},{"issue":"1","key":"e_1_2_10_27_1","first-page":"128","article-title":"Kinetics of cell growth and cyclosporin A production by Tolypocladium inflatum when scaling up from shake flask to bioreactor","volume":"18","author":"El Enshasy H.","year":"2008","journal-title":"Journal of Microbiology and Biotechnology"},{"key":"e_1_2_10_28_1","unstructured":"Espacenet\u2010patent search. (2021). Worldwide.espacenet.com.https:\/\/worldwide.espacenet.com\/"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2012.28"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/vr.102484"},{"key":"e_1_2_10_31_1","first-page":"15","volume-title":"Molecular actions of cyclosporin A, FK 506 and rapamycin Immunosuppressive drugs: developments in anti\u2010rejection therapy","author":"Fruman D.","year":"1994"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbt.2014.07.006"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2022.103108"},{"key":"e_1_2_10_34_1","unstructured":"Global mTOR (Mammalian target of rapamycin) Inhibitors Market 2019\u20132023. (2019).Technavio. Retrieved April 23 202.https:\/\/www.technavio.com\/report\/global\u2010mtor-mammalian-target-of-rapamycin-inhibitors-market-industry-analysis"},{"key":"e_1_2_10_35_1","unstructured":"Global mTOR Inhibitors Market by Type (Rapamune Torisel Afinitor Zortress) By Application (Tumor Treatment Kidney Transplant Others) And By Region (North America Latin America Europe Asia Pacific and Middle East & Africa) Forecast From 2022 To 2030 (2020).Dataintelo. Retrived April 20 2021.https:\/\/dataintelo.com\/report\/global-mtor-inhibitors-market\/"},{"key":"e_1_2_10_36_1","unstructured":"Global Organ Transplant Immunosuppressant Market 2017\u20132021. (2021).https:\/\/www.researchandmarkets.com\/reports\/4328289\/global-organ-transplant-immunosuppressant-market\/"},{"key":"e_1_2_10_37_1","unstructured":"Global Organ Transplant Immunosuppressant Market to Grow at a CAGR of 3.8% by 2021 Research and Markets Forecasts.The Free Library. (2014). Accesed April 20 2022.https:\/\/www.thefreelibrary.com\/Global+Organ+Transplant+Immunosuppressant+Market+to+Grow+at+a+CAGR+of...\u2010a0498879340"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.059600"},{"key":"e_1_2_10_39_1","first-page":"825","article-title":"Richerche batteriologiche e chemiche sulle alterazoni del mais","volume":"7","author":"Gosio B.","year":"1896","journal-title":"Riv d'Igiene Sanita Pub Ann"},{"key":"e_1_2_10_40_1","unstructured":"Goto T. Kino T. Okuhara M. Tanaka H. Tsurumi Y. &Takase S.(1995). Production of cyclosporin A and\/or C with a strain of NECTRIA. U.S. Patent No. 5 447 854. Washington DC: U.S. Patent and Trademark Office."},{"key":"e_1_2_10_41_1","unstructured":"Grand View Research. (2021). Organ Transplant Immunosuppressant Drugs.https:\/\/www.prnewswire.com\/news-releases\/organ-transplant-immunosuppressant-drugs-market-worth-5-88-billion-by-2026-grand-view-research-inc-300942663.html\/"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00073a083"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2859-12-52"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-013-1301-7"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(96)00770-4"},{"key":"e_1_2_10_46_1","unstructured":"Immunology Market Trends Size Share & Global Outlook 2026. (2021).https:\/\/www.fortunebusinessinsights.com\/industry-reports\/immunology-market-100657\/"},{"key":"e_1_2_10_47_1","unstructured":"Immunosuppressant Drugs Market Growth Trends and Forecast. (2021).https:\/\/www.mordorintelligence.com\/industry-reports\/immunosuppressant-drugs-market\/"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.2165\/00128071-200910040-00003"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo951646q"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-016-8052-0"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274\u2010014-1685-1"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1590\/s1517-83822010000400033"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2021.106036"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00296a042"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00185a071"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-009-0634-8"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-011-3348-6"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/gels8020129"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-013-4716-1"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1263\/jbb.105.418"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1333314"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2011.11.003"},{"key":"e_1_2_10_63_1","unstructured":"Kumar P. Malviya H. K. Maurya R. K. &Shukla A.(2008).\u00a0Fermentation processes for the preparation of tacrolimus. U.S. Patent Application No. 12\/089 279."},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.4014\/mbl.2001.0100"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025924"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.0811.629"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/31.2.196"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.21180"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-968517"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.4103\/2229-5178.105488"},{"key":"e_1_2_10_71_1","unstructured":"Market watch. (2021).https:\/\/www.marketwatch.com\/press-release\/immunosuppressive-drugs-market-2018-2025overview-and-scope-industry-outlook-size-forecast-2019-10-16\/"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-012-4364-x"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200666170-00010"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2006.01270.x"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10847-010-9870-9"},{"issue":"4","key":"e_1_2_10_76_1","first-page":"419","article-title":"Optimization of process parameters for tacrolimus (FK 506) production by new isolate of Streptomyces sp. using response surface methodology (RSM)","volume":"3","author":"Mishra A.","year":"2012","journal-title":"Journal of Biochemical Technology"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-009-0635-7"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-012-4413-5"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.3839\/jabc.2016.050"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1080\/10826068.2017.1303609"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.btre.2"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006197804888"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.17.5243-5248.1996"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0032-9592(98)00095-8"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.8.3.321"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1080\/00021369.1988.10868854"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1053\/jlts.2001.24645"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00063a093"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2018.08.014"},{"key":"e_1_2_10_90_1","unstructured":"Organ Transplant Immunosuppressant Drugs Market Size Report 2026. (2021).https:\/\/www.grandviewresearch.com\/industry-analysis\/organ-transplant-mmunosuppressant-drugs-market\/"},{"key":"e_1_2_10_91_1","unstructured":"Organ Transplant Immunosuppressant Drugs Market Worth $5.88 Billion By 2026. Grandviewresearch.com (2021).https:\/\/www.grandviewresearch.com\/press-release\/global-organ-transplant-immunosuppressant-drugs-market\/(Accessed 20 April 2021)."},{"issue":"1","key":"e_1_2_10_92_1","first-page":"18","article-title":"The emergence of mycophenolate mofetilin dermatology: from its roots in the world of organ transplantation to its versatile role in the dermatology treatment room","volume":"4","author":"Park H.","year":"2011","journal-title":"The Journal of Clinical and Aesthetic Dermatology"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2009.06.021"},{"key":"e_1_2_10_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2010.71"},{"key":"e_1_2_10_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcab.2020.101803"},{"key":"e_1_2_10_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.btre.2016.07.003"},{"key":"e_1_2_10_97_1","unstructured":"De Pater R. M.(2012).\u00a0Method for the purification of mycophenolate mofetil U.S. Patent No. 8 273 739. Washington DC: U.S. Patent and Trademark Office."},{"key":"e_1_2_10_98_1","unstructured":"Polavarapu B. R. Battula S. K. Adibhatla K. S. B. R. & Nannapaneni V. C. (2016). cffice."},{"key":"e_1_2_10_99_1","doi-asserted-by":"publisher","DOI":"10.1128\/aem.71.1.550-553.2005"},{"key":"e_1_2_10_100_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2672.2006.02855.x"},{"key":"e_1_2_10_101_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740330902969441"},{"key":"e_1_2_10_102_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-013-5384-x"},{"key":"e_1_2_10_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2015.11.009"},{"key":"e_1_2_10_104_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00070a058"},{"key":"e_1_2_10_105_1","unstructured":"Rudat W. R. Bormann E. J. &Arnold G.(1993).\u00a0Process for making and isolating cyclosporin a by fermentation. U.S. Patent No. 5 256 547. Washington DC: U.S. Patent and Trademark Office."},{"key":"e_1_2_10_106_1","doi-asserted-by":"crossref","unstructured":"Russell G. Graveley R. Seid J. Al\u2010Humidan A. K. &Skjodt H.(1992).Mechanisms of action of cyclosporine and effects on connective tissues.InSeminars in Arthritis and Rheumatism 16\u201322.https:\/\/doi.org\/10.1016\/0049-0172(92)90009-3","DOI":"10.1016\/0049-0172(92)90009-3"},{"key":"e_1_2_10_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2010.05.007"},{"key":"e_1_2_10_108_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-014-5595-9"},{"key":"e_1_2_10_109_1","doi-asserted-by":"publisher","DOI":"10.2323\/jgam.49.321"},{"key":"e_1_2_10_110_1","doi-asserted-by":"publisher","DOI":"10.1080\/00021369.1981.10864674"},{"key":"e_1_2_10_111_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119251316"},{"key":"e_1_2_10_112_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1702904"},{"key":"e_1_2_10_113_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104116"},{"key":"e_1_2_10_114_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-99-24281"},{"key":"e_1_2_10_115_1","doi-asserted-by":"publisher","DOI":"10.3920\/wmj2013.1619"},{"key":"e_1_2_10_116_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-1345(03)00211-2"},{"key":"e_1_2_10_117_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3458.2008.00036.x"},{"key":"e_1_2_10_118_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5173(00)00617-7"},{"key":"e_1_2_10_119_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-765x.2009.02652.x"},{"key":"e_1_2_10_120_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678-4324-2016160366"},{"key":"e_1_2_10_121_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)73331-4"},{"key":"e_1_2_10_122_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00124a043"},{"key":"e_1_2_10_123_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.4.12.2325"},{"key":"e_1_2_10_124_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11164-015-2215-y"},{"key":"e_1_2_10_125_1","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.1001.01006"},{"key":"e_1_2_10_126_1","unstructured":"Survase S. A. Bankar S. B. Annapure U. S. &Singhal R. S.(2015). The effect of agitation and aeration on production of cyclosporin A in batch cultures ofTolypocladium inflatumMTCC 557."},{"key":"e_1_2_10_127_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2011.03.004"},{"key":"e_1_2_10_128_1","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.0805.324"},{"key":"e_1_2_10_129_1","unstructured":"The cyclosporine story. (2021).https:\/\/www.davidmoore.org.uk\/Sec.04_01.htm\/"},{"key":"e_1_2_10_130_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199512000-00007"},{"key":"e_1_2_10_131_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.42.591"},{"key":"e_1_2_10_132_1","doi-asserted-by":"publisher","DOI":"10.9790\/3013-0407066075"},{"key":"e_1_2_10_133_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.enzmictec.2012.08.008"},{"key":"e_1_2_10_134_1","unstructured":"Vaid S. & Narula P.(2007).Process for producing tacrolimus (FK\u2010506) using vegetable oil as sole source of carbon. U.S. Patent Application No. 11\/698 881."},{"key":"e_1_2_10_135_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10438-005-0015-7"},{"key":"e_1_2_10_136_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-018-9177-0"},{"key":"e_1_2_10_137_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-017-1974-4"},{"key":"e_1_2_10_138_1","article-title":"Insights on the global immunosuppressants market (2019 to 2026) \u2010 by drug class, calcineurin inhibitors, indication, and distribution channel \u2010 ResearchAndMarkets.com","author":"Wire B.","year":"2022","journal-title":"Businesswire.com"},{"key":"e_1_2_10_139_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24941"},{"key":"e_1_2_10_140_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-005-8463-y"},{"key":"e_1_2_10_141_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-021-03144-8"},{"key":"e_1_2_10_142_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13765-014-4207-9"},{"key":"e_1_2_10_143_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02884035"},{"key":"e_1_2_10_144_1","unstructured":"Zion. (2021).https:\/\/www.zionmarketresearch.com\/report\/organ-transplant-immunosuppressant-drugs-market\/"},{"key":"e_1_2_10_145_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00351a005"},{"key":"e_1_2_10_146_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13213-012-0597-2"}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.28231","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bit.28231","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.28231","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T23:43:49Z","timestamp":1760053429000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.28231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,8]]},"references-count":145,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/bit.28231"],"URL":"https:\/\/doi.org\/10.1002\/bit.28231","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"value":"0006-3592","type":"print"},{"value":"1097-0290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,8]]},"assertion":[{"value":"2021-11-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}