New way to make yeast hybrids may inspire new brews and biofuels

About 500 years ago, the acci­dent­al nat­ur­al hybrid­iz­a­tion of Sac­char­o­my­ces cerevisi­ae, the yeast respons­ible for things like ale, wine and bread, and a dis­tant yeast cous­in gave rise to lager beer. Today, cold-brewed lager is the world’s most con­sumed alco­hol­ic bever­age, fuel­ing an industry with annu­al sales of more than $250 billion. The first lagers depended on the serendip­it­ous cross of Sac­char­o­my­ces spe­cies as evol­u­tion­ar­ily diverse as humans and chick­ens. The res­ult, how­ever, yiel­ded a product of enorm­ous eco­nom­ic value, demon­strat­ing the lat­ent poten­tial of inter­spe­cies yeast hybrids. In nature, the odds of a sim­il­ar hybrid­iz­a­tion event are, con­ser­vat­ively, one in a bil­lion. Now, thanks to a new meth­od for mak­ing inter­spe­cies yeast hybrids in the lab, the makers of beer, wine, bio­fuels and oth­er products that depend on yeasts may soon have many more strains of the microor­gan­ism to work with. ​“We can achieve hybrids at rates of one in a thou­sand cells,” notes Wil­li­am Alex­an­der, a Uni­ver­sity of Wis­con­sin-Madis­on postdoc­tor­al research asso­ci­ate and the lead author of a paper describ­ing the new meth­od in a spe­cial syn­thet­ic bio­logy issue of the journ­al Fungal Genet­ics and Bio­logy. ​“It is much more effi­cient than nature.” There are hun­dreds of known spe­cies of yeasts and they occupy almost every eco­lo­gic­al niche ima­gin­able world­wide. They are essen­tial to the pro­cess of fer­ment­a­tion, where the microbes con­vert sug­ars to alco­hol and car­bon diox­ide. Yeasts are used widely to not only make beer, wine and bread, but also cider, whis­key, cheese, yogurt, soy sauce and an array of oth­er fer­men­ted foods and bever­ages. In industry, yeasts are used to pro­duce bio­fuels and to make enzymes, fla­vors and pig­ments and even drugs such as human insulin. An abil­ity to quickly and effi­ciently churn out new yeast inter­spe­cies hybrids means indus­tries that depend on yeasts will have many more organ­isms to exper­i­ment with to make new fla­vors, enhance pro­duc­tion and pro­duce entirely new products, explains Chris Todd Hit­tinger, a UW-Madis­on pro­fess­or of genet­ics and the seni­or author of the new study. For example, the happy mar­riage of Sac­char­o­my­ces cerevisi­ae and its dis­tant cous­in Sac­char­o­my­ces eubay­anus, a spe­cies that inhab­its tree galls in nature, per­mit­ted the cold-tem­per­at­ure fer­ment­a­tion that made lager beer pos­sible. The new yeast hybrid­iz­a­tion meth­od uses plas­mids, circles of DNA that can be built into an organ­ism to con­fer a genet­ic qual­ity. In the lab, plas­mids are routinely used to manip­u­late genes in cells. Genes in the plas­mids facil­it­ate yeast hybrid­iz­a­tion by express­ing a nat­ur­ally occur­ring yeast pro­tein that allows two dis­tinct spe­cies of yeasts to mate. ​“The advant­ages of the tech­nique are speed, effi­ciency, and pre­ci­sion,” says Hit­tinger, a world author­ity on yeast genet­ics and a co-dis­cover­er of the wild Patago­ni­an yeast that formed the lager beer hybrid. ​“With­in a week, you can gen­er­ate a large num­ber of hybrids of whatever two spe­cies you want, cre­at­ing forms nev­er seen before.” The new study describes four new hybrids, one of which was made using a strain of Sac­char­o­my­ces eubay­anus dis­covered near She­boy­gan, Wis­con­sin, after Hit­tinger and his col­leagues first found the lager yeast par­ent in the alpine regions of Patago­nia. The new hybrid is being tested in a new beer recipe in the UW-Madis­on Depart­ment of Food Sci­ence. The new tech­nique may also help industry over­come a cre­at­ive bot­tle­neck, as many indus­tri­al strains of yeasts are sterile, unable to pro­duce spores. ​“If you have a favor­ite ale strain, for example, you should eas­ily be able to hybrid­ize it with a wild strain using this meth­od,” Hit­tinger says. ​“There is a lot of poten­tial out there for new fla­vors and com­bin­a­tions.” Finally, the plas­mids used to facil­it­ate the pro­cess of hybrid­iz­a­tion can be removed from the new hybrid yeasts, leav­ing the gen­omes of the two fused organ­isms unchanged. In addi­tion to Alex­an­der and Hit­tinger, authors of the new study include Dav­id Per­is, Brandon T. Pfannen­stiel, Dana A. Opu­lente and Mei­hua Kuang, all from UW-Madis­on. The new study was sup­por­ted by grants from the Nation­al Sci­ence Found­a­tion and the Depart­ment of Energy through the Great Lakes Bioen­ergy Research Cen­ter.

Ori­gin­al publication

Wil­li­am G. Alex­an­der, Dav­id Per­is, Brandon T. Pfannen­stiel, Dana A. Opu­lente, Mei­hua Kuang, Chris Todd Hit­tinger. Effi­cient engin­eer­ing of mark­er-free syn­thet­ic allotet­raploids of Sac­char­o­my­ces. Fungal Genet­ics and Bio­logy, 2015; DOI: 10.1016/j.fgb.2015.11.002 Source: © Uni­ver­sity of Wis­con­sin (by Terry Devitt)