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==Alternative sources== Because of the limited availability of mammalian stomachs for rennet production, cheese makers have sought other ways to coagulate milk since at least [[Ancient Rome|Roman]] times. The many sources of enzymes that can be a substitute for animal rennet range from plants and fungi to microbial sources.<ref name="EFSA">{{Cite web |url=https://www.efsa.europa.eu/en/supporting/pub/en-689 |title=TECHNICAL REPORT OF EFSA: Explanatory Note for the Guidance of the Scientific Panel of Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) on the Submission of a Dossier on Food Enzymes: 3.2. Source Materials and Manufacturing Process: Comments/Explanations: Updated on version 2014:EN-579 |publisher=[[European Food Safety Authority]] |access-date=2015-11-11 |date=2014-11-14 }}</ref> Cheeses produced from any of these varieties of rennet are suitable for [[lacto vegetarianism|lactovegetarians]], as well as those keeping [[Kashrut|Kosher]]. Fermentation-produced [[chymosin]] is used more often in industrial cheesemaking in North America and Europe today because it is less expensive <!-- and of higher quality --> than animal rennet.<ref name="GMO Database">{{cite web|url=http://www.gmo-compass.org/eng/database/enzymes/83.chymosin.html|publisher=GMO Compass|title=Chymosin|access-date=2011-03-03|url-status=dead|archive-url=https://web.archive.org/web/20150326181805/http://www.gmo-compass.org/eng/database/enzymes/83.chymosin.html|archive-date=2015-03-26}}</ref> === Vegetable === Many plants have coagulating properties. [[Homer]] suggests in the ''[[Iliad]]'' that the Greeks used an extract of [[ficus|fig]] juice to coagulate milk.<ref>{{cite book | author1 = P. F. Fox | author2 = Paul McSweeney | author3 = Timothy M. Cogan | author4 = Timothy P. Guinee | year = 2004 | title = Cheese: Major cheese groups | pages = 2 | publisher = Academic Press | isbn = 978-0-12-263652-3 | url = https://books.google.com/books?id=vz-2Y7npqj0C&q=fig&pg=PA2 | access-date = 2009-05-06 }}</ref> Other examples include several species of [[Galium]], [[Caper|dried caper leaves]],<ref>Mike, Tad, "Capers: The Flower Inside", Epikouria Magazine, Fall/Winter 2006</ref> [[Urtica|nettles]], [[thistle]]s, [[Malva|mallow]], ''[[Withania coagulans]]'' (also known as Paneer Booti, Ashwagandh and the Indian Cheesemaker), and [[Glechoma hederacea|ground ivy]]. Some traditional cheese production in the [[Mediterranean]] uses enzymes from thistle or ''[[Cynara]]'' (artichokes and cardoons). Phytic acid, derived from unfermented [[soy]]beans, or fermentation-produced chymosin (FPC) may also be used.{{Citation needed|date=January 2021}} [[Vegetable]] rennet might be used in the production of [[Kosher foods|kosher]] and [[halal]] cheeses, but nearly all kosher cheeses are produced with either microbial rennet or FPC.{{citation needed|date=January 2013}} <!-- Worldwide, there is no industrial production for vegetable rennet. --> Commercial so-called vegetable rennets usually contain an extract from the [[Mold (fungus)|mold]] ''[[Rhizomucor miehei]]'' described below.{{Citation needed|date=January 2021}} === Microbial === Some molds such as ''[[Rhizomucor miehei]]'' are able to produce [[Proteolysis|proteolytic]] enzymes.<ref>{{Cite journal | last1 = Preetha | first1 = S. | last2 = Boopathy | first2 = R. | journal = World Journal of Microbiology and Biotechnology | volume = 13 | issue = 5 | pages = 573 | year = 1997 | doi = 10.1023/A:1018525711573 |title=Purification and characterization of a milk clotting protease from Rhizomucor miehei| s2cid = 85375727 }}</ref> These molds are produced in a [[fermenter]] and then specially concentrated and purified to avoid contamination with unpleasant byproducts of the mold growth.<ref name="Microbial Rennet">{{cite book |last1=K Ruby Blume |title=Everyday Cheesemaking: How to Succeed Making Dairy and Nut Cheese at Home |date=1 July 2014 |publisher=Microscosm Publishing |isbn=978-1-62106-592-0 |page=116 |url=https://books.google.com/books?id=2g94CAAAQBAJ&pg=PA116}}</ref> The traditional view is that these coagulants result in bitterness and low yield in cheese, especially when aged for a long time. Over the years{{when|date=September 2019}}, microbial coagulants have improved greatly, largely due to the [[characterization (materials science)|characterization]] and purification of secondary enzymes responsible for bitter peptide formation/non-specific proteolytic breakdown in cheese aged for long periods. Consequently, it has become possible to produce several high-quality cheeses with microbial rennet.<ref>{{cite web|url=http://www.bmbtrade.it/img/1421845498_MarzymeTM.pdf|title=Marzyme Microbial Coagulant|website=BMBtrade.it|date=2011|access-date=2017-07-17|archive-date=2016-05-03|archive-url=https://web.archive.org/web/20160503220141/http://bmbtrade.it/img/1421845498_MarzymeTM.pdf|url-status=dead}}</ref> It is also suitable for the elaboration of [[vegan]] cheese, provided no animal-based ingredients are used in its production.<ref>{{Cite web|title=How to Know if Your Cheese Is Vegetarian Friendly|url=https://www.thespruceeats.com/what-is-vegetarian-rennet-591572|access-date=2021-10-23|website=The Spruce Eats|language=en}}</ref> === Fermentation-produced chymosin=== Because of the above imperfections of microbial and animal rennets, many producers sought other replacements of rennet. With genetic engineering it became possible to isolate rennet genes from animals and introduce them into certain [[bacteria]], [[fungi]], or [[yeast]]s to make them produce [[recombinant protein|recombinant]] chymosin during fermentation. The genetically modified microorganism is killed after fermentation and chymosin isolated from the fermentation broth, so that the fermentation-produced [[chymosin]] (FPC) used by cheese producers does not contain a GMO or any GMO DNA. FPC is identical to chymosin made by an animal, but is produced in a more efficient way. FPC products have been on the market since 1990 and, because the quantity needed per unit of milk can be standardized, are commercially viable alternatives to crude animal or plant rennets, as well as generally preferred to them in industrial production.<ref name="Law 2010 100β101">{{cite book|last=Law|first=Barry A.|title=Technology of Cheesemaking|year=2010|publisher=WILEY-BLACKWELL|location=UK|isbn=978-1-4051-8298-0|pages=100β101|url=http://eu.wiley.com/WileyCDA/WileyTitle/productCd-1405182989.html}}</ref> Originally created by biotechnology company [[Pfizer]], FPC was the first artificially-produced enzyme to be registered and allowed by the [[US Food and Drug Administration]].<ref>{{cite news|title=FDA Approves 1st Genetically Engineered Product for Food|url=https://www.latimes.com/archives/la-xpm-1990-03-24-mn-681-story.html|access-date=1 May 2014|newspaper=[[Los Angeles Times]]|date=24 March 1990}}</ref><ref name=chymosinCase>Staff, National Centre for Biotechnology Education, 2006. [https://archive.today/20121223101343/http://www.ncbe.reading.ac.uk/NCBE/GMFOOD/chymosin.html Case Study: Chymosin]</ref> In 1999, about 60% of US [[hard cheese]]s were made with FPC,<ref name="USDA">{{cite web |url=https://fpc.state.gov/6176.htm|title=Food Biotechnology in the United States: Science, Regulation, and Issues|publisher=U.S. Department of State|access-date=2006-08-14}}</ref> and it has up to 80% of the global market share for rennet.<ref>E. Johnson, J. A. Lucey (2006) [https://www.ncbi.nlm.nih.gov/pubmed/16537950 Major Technological Advances and Trends in Cheese] J. Dairy Sci. 89(4): 1174β1178</ref> By 2017, FPC takes up 90% of the global market share for rennet.<ref name="johnson2017">{{cite journal | last=Johnson | first=M.E. | title=A 100-Year Review: Cheese production and quality | journal=Journal of Dairy Science | volume=100 | issue=12 | year=2017 | issn=0022-0302 | doi=10.3168/jds.2017-12979 | pages=9952β9965|pmid=29153182|url=https://www.journalofdairyscience.org/article/S0022-0302(17)31054-8/fulltext| doi-access=free }}</ref> The most widely used FPC is produced either by the fungus ''[[Aspergillus niger]]'' and commercialized under the trademark CHY-MAX<ref>{{cite web|url=http://www.chr-hansen.com/products/product-areas/enzymes/our-product-offering.html|title=Enzymes for Cheese|work=Chr-Hansen.com|archive-url=https://web.archive.org/web/20111101092309/http://www.chr-hansen.com/products/product-areas/enzymes/our-product-offering.html|archive-date=2011-11-01|access-date=2012-07-30}}</ref> by the Danish company [[Chr. Hansen]], or produced by ''[[Kluyveromyces lactis]]'' and commercialized under the trademark Maxiren by the Dutch company DSM.<ref>{{cite web |url=http://www.dsm.com/le/en_US/foodspecialties/html/Products_Maxiren.htm |title=DSM Food Specialties β Product Page β Maxiren |website=DSM.com |access-date=2013-01-28 |url-status=dead |archive-url=https://web.archive.org/web/20120106010450/http://www.dsm.com/le/en_US/foodspecialties/html/Products_Maxiren.htm |archive-date=2012-01-06 }}</ref> FPC is chymosin B, so it is purer than animal rennet, which contains a multitude of proteins. FPC provides several benefits to the cheese producer compared with animal or microbial rennet: higher production yield, better curd texture, and reduced bitterness.<ref name="Law 2010 100β101"/> Cheeses produced with FPC can be certified kosher<ref>{{cite web|url=http://www.kashrut.com/articles/cheese/|title=Say Cheese!}}</ref><ref name=Chymax>{{cite web|url=https://www.thecheesemaker.com/pdf/Chymosin_Rennet_Specs.pdf|title=Chymax spec sheet}}</ref> and halal,<ref name=Chymax /> and are suitable for vegetarians if no animal-based alimentation was used during the chymosin production in the fermenter.{{Citation needed|date=January 2021}}
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