(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/038617 Al 17 March 2016 (17.03.2016) P O P C T (51) International Patent Classification: Rachel; P.O. Box 116, 3600500 Alonei Abba (IL). CO¬ C12N 9/02 (2006.01) C12P 19/18 (2006.01) HEN, Shahar; 7/14 Bialik Street, 7526812 Rishon-LeZion C12N 9/14 (2006.01) C12P 19/56 (2006.01) (IL). PORTNOY, Vitaly; 8 HaChazav Street, Apartment C12N 9/90 (2006.01) C12N 15/54 (2006.01) 1, 3683208 Nesher (IL). DORON-FAIGENBOIM, Adi; C12N 15/79 (2006.01) 122 Ben-Gurion Street, 4732135 Ramat-HaSharon (IL). PETREIKOV, Marina; 55/22 Bernstein Street, 7550355 (21) International Application Number: Rishon-LeZion (IL). SHEN, Shmuel; 67 HaRimon Street, PCT/IL2015/050933 7680300 Moshav Beit-Elazari (IL). TADMOR, Yaakov; (22) International Filing Date: 11 Hadas Street, P.O. Box 309, 3657600 Timrat (IL). 10 September 2015 (10.09.201 5) BURGER, Yosef; 29a HaTichon Street, 3229619 Haifa (IL). LEWINSOHN, Efraim; 32 Moran Street, 3657600 (25) Filing Language: English Timrat (IL). KATZIR, Nurit; 50 Yizrael Street, 3603250 (26) Publication Language: English Kiryat-Tivon (IL). SCHAFFER, Arthur A.; 16 HaZayit Street, 73 12700 Hashmonaim (IL). OREN, Elad; P.O. (30) Priority Data: Box 216, Beit Shearim, 3657800 Doar-Na Haluza (IL). 62/048,924 11 September 2014 ( 11.09.2014) US 62/089,929 10 December 2014 (10. 12.2014) US (74) Agents: EHRLICH, Gal et al; G.E. Ehrlich (1995) Ltd., 11 Menachem Begin Road, 5268104 Ramat Gan (IL). (71) Applicant: THE STATE OF ISRAEL, MINISTRY OF AGRICULTURE & RURAL DEVELOPMENT, AGRI¬ (81) Designated States (unless otherwise indicated, for every CULTURAL RESEARCH ORGANIZATION (ARO) kind of national protection available): AE, AG, AL, AM, (VOLCANI CENTER) [IL/IL]; P.O. Box 6, 5025001 AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, Beit-Dagan (IL). BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (72) Inventors: ITKIN, Maxim; Kibbutz HaOgen, 4288000 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, Doar-Na Emek Hefer (IL). DAVIDOVICH-RIKANATI, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, [Continued on nextpage] (54) Title: METHODS OF PRODUCING MOGROSIDES AND COMPOSITIONS COMPRISING SAME AND USES THEREOF (57) Abstract: Isolated mogroside and mogrol biosynthetic pathway enzyme FIG. 2 polypeptides useful in mogroside biosynthesis are provided. Mogroside bio synthetic pathway enzymes of the invention include squalene epoxidase (SE), expoxy hydratase (EH), cytochrome p450 (Cyp), cucurbitadienol synthase (CDS) and udp-glucosyl-transferase (UGT), Also provided are methods of producing a mogroside using the isolated mogroside and mogrol biosynthetic enzyme polypeptides, the methods comprising contacting a mogrol and/or a glycosylated mogrol (mogroside) with at least one UDP glucose glucosyl transferase (UGT) enzyme polypeptide of the invention catalyzing glucosyla- tion of the mogrol and/or the glucosylated mogrol to produce a mogroside with an additional glucosyl moietie(s), thereby producing the mogroside. Al j ternatively or additionally provided is a method of synthesizing a mogrol, the method comprising contacting a mogrol precursor substrate with one or more mogrol biosynthetic pathway enzyme polypeptides as described herein cata lyzing mogrol synthesis from the mogrol precursor substrate, thereby syn l ™ thesizing the mogrol. < 00 © v o o WO 2016/038617 Al II N I I NIMH IM MM l lllll ll Ml MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. Published: — with international search report (Art. 21(3)) (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, — before the expiration of the time limit for amending the GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, claims and to be republished in the event of receipt of TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, amendments (Rule 48.2(h)) TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, — with sequence listing part of description (Rule 5.2(a)) DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, METHODS OF PRODUCING MOGROSIDES AND COMPOSITIONS COMPRISING SAME AND USES THEREOF FIELD AND BACKGROUND OF THE INVENTION The present invention, in some embodiments thereof, relates to methods of producing mogrosides and compositions comprising same and uses thereof. Mogrosides are triterpene-derived specialized secondary metabolites found in the fruit of the Cucurbitaceae family plant Siraitia grosvenorii (Luo Han Guo). Their biosynthesis in fruit involves number of consecutive glucosylations of the aglycone mogrol to the final sweet products mogroside V and mogroside VI (Figure 1). Mogroside V has been known in the food industry as a natural non-sugar food sweetener, with a sweetening capacity of -250 times that of sucrose (Kasai R., et al., Sweet cucurbitane glycosides from fruits of Siraitia siamensis (chi-zi luo-han-guo), a Chinese folk medicine. Agric Biol Chem 1989, 53(12):3347-3349.). Moreover, additional health benefits of mogrosides have been revealed in recent studies (Li et al., Chemistry and pharmacology of Siraitia grosvenorii: a review. Chin J Nat Med. 2014 12(2):89-102.). The parent aglycone compound mogrol is derived by successive hydroxylations of cucurbitadienol, the initial product of the stereospecific triterpene synthase, cucurbitadienol synthase. Cucurbitadienol is subsequently hydroxylated, by as yet undetermined enzymes, at the Cll, C24 and C25 positions, leading to mogrol (Figure 1). The trans C24,C25 di-hydroxylations are rare among the triterpenoid cucurbitadienol derivatives (Chen JC, et al., Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat. Prod. Rep. 2005, 22, 386-399) and thus makes the identification of the enzymes responsible a challenge. The mogrol is subsequently glucosylated at the C3 and C24 positions to varying degrees, from 1 to 6 glucosyl groups, in a temporally successive pattern during fruit development and the glucosylated mogrol compounds are termed mogrosides. The sweetness strength of the mogrosides increases with the additional glucose moieties such that M6 (with 6 glucosyl groups) is sweeter than M5, followed by M4, respectively (Kasai R., et al., Sweet cucurbitane glycosides from fruits of Siraitha siamensis (chi-zi luo-han-guo), a Chinese folk medicine. Agric Biol Chem 1989, 53(12):3347-3349). The purified mogroside V, has been approved as a high-intensity sweetening agent in Japan (Jakinovich, W., Jr., Moon, C , Choi, Y. H., & Kinghorn, A. D. 1990. Evaluation of plant extracts for sweetness using the Mongolian gerbil. Journal of Natural Products, 53, 190-195) and the extract has gained generally recognized as safe (GRAS) status in the USA as a non-nutritive sweetener and flavor enhancer. Extraction of mogrosides from the fruit can yield a product of varying degrees of purity, often accompanied by undesirable aftertaste. In addition, yields of mogroside from cultivated fruit are limited due to low plant yields and particular cultivation requirements of the plant. It is therefore advantageous to be able to produce sweet mogroside compounds via biotechnological processes. Additional background art includes: WO20 13/076577 discloses enzymes of the UGT family (UDPglucose glycosyl transferase) from Arabidopsis thaliana and Stevia rebaudiana, plants which do not naturally produce mogroside. Four of these enzymes were capable of performing glycosylation of the aglycone mogrol, specifically the addition of single glucose moieties at the C24 positions to produce Mlb. The fifth enzyme UGT73C5 from Stevia rebaudiana showed glycosylation at both C3 and C24. WO 2014086842 discloses the cucurbitadienol synthase, the cyp450 that catalyzes C-11 OH production and some UGT polypeptides from Siraitia grosvenorii, shows that these enzymes function in yeast, and provide as well for methods for producing mogrosides. In addition, they also disclose 2 epoxide hydrolases, and demonstrate their ability to hydrate epoxysqualene, suggesting that they can hydrate epoxy cucurbitadienol as well. In particular the invention proposes various biosynthetic pathways useful for mogroside production and enzymes useful for mogroside production are provided. Furthermore, the invention provides recombinant hosts useful in performing the methods of the invention.Tang et a , An efficient approach to finding Siraitia grosvenorii triterpene biosynthetic genes by RNA-seq and digital gene expression analysis. BMC Genomics. 2011; 12: 343. SUMMARY OF THE INVENTION According to an aspect of some embodiments of the present invention there is provided an isolated uridine diphospho-glucosyl transferase enzyme (UGT) polypeptide comprising an amino acid sequence, wherein the polypeptide catalyzes primary glucosylation of mogrol at C24 and primary glucosylation of mogroside at C3. According to some embodiments of the present invention the isolated UGT polypeptide catalyzes: (a) primary glucosylation of mogrol at C24; (b) primary glucosylation of mogroside at C3; and (c) branching glucosylation of mogroside at C3. According to some embodiments of the present invention the amino acid sequence at least 34% identical to SEQ ID NO: 34. According to some embodiments of the present invention the amino acid sequence is as set forth in SEQ ID NO: 34. According to an aspect of some embodiments of the present invention there is provided an isolated uridine diphospho-glucosyl transferase enzyme (UGT) polypeptide comprising an amino acid sequence, wherein the polypeptide catalyzes branching glucosylation of mogroside at the (1-2) and (1-6) positions of C3 and branching glucosylation of mogroside at the (1-2) and (1-6) positions of C24.