Electronic Supplementary Material (ESI) for Chemical Science. This journal is © The Royal Society of Chemistry 2018

Electric Supporting Information (ESI)

Crystal structure and functional analysis of large-terpene synthase belonging to a newly found subclass

Masahiro Fujihashi,a* Tsutomu Sato,b* Yuma Tanaka,a Daisuke Yamamoto,a Tomoyuki Nishi,b Daijiro Ueda,b Mizuki Murakami,b Yoko Yasuno,c Ai Sekihara,c Kazuma Fuku,c Tetsuro Shinadac & Kunio Mikia*

a. Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan. E-mail: [email protected], [email protected] b. Department of Applied Biological Chemistry, Faculty of Agriculture, and Graduate School of Science and Technology, Niigata University, 8050 Ikarashi-2, Niigata 950-2181, Japan. E-mail: [email protected] c. Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi, Osaka 558-8585, Japan.

S1 Table of Contents

Experimental Procedures S3 General procedure S3 Vector construction, expression and purification of BalTS S3 Crystallization and crystallographic analysis of balTS S3 Oligomeric state analysis S4 Analysis of the dimer geometry S4 Vector construction, expression and purification of BsuTS S4 Homology modeling of BsuTS S4 Enzymatic assays S5 Isolation and identification of β-springen S5

Movie Captions S6 Author Contributions S6

Figures Fig. S1 S7 Fig. S2 S8 Fig. S3 S9 Fig. S4 S10 Fig. S5 S17 Fig. S6 S18 Fig. S7, S8 S19 Fig. S9 S20 Fig. S10 S21 Fig. S11 S22

Tables Table S1 S23 Table S2 S24

References S27

S2 Experimental Procedures General procedure NMR spectra were recorded using a Bruker DPX 400 spectrometer at 400 MHz for proton (1H) and 100 MHz for carbon (13C). GC-MS was performed on a JMS-T100GCV spectrometer (JEOL) equipped with a DB-1 capillary column (30 m  0.25 mm  0.25 µm; J&W Scientific), using the EI mode operated at 70 eV. GC analyses were performed on a Shimadzu GC-2014 chromatograph equipped with a flame ionization detector and a DB-1 capillary column.

Vector construction, expression and purification of BalTS The BalTS expression vectors (wild-type as well as the D85A, D88A, D92A, D249A, D253A, and D257A mutants) were constructed by Genewiz (South Plainfield, NJ, USA) as follows. DNA fragments optimized for BalTS (WP_003323837.1) expression by E. coli were synthesized. The DNA fragments contain the codons to express the peptide HMSSGLVPRGSH prior to the BalTS sequence. The first His and the second Met corresponds to the NdeI restriction site (DNA: CATATG). Residues SSGLVPRGSH correspond to the amino-acid residues around the thrombin digestion site appearing in pET14b, pET15b and pET28a-c. The synthesized DNA fragments were inserted between the NdeI and the BamHI sites of the pCold-II plasmid. The constructed vectors express translation enhancing element (TEE), His6-tag and thrombin digestion sites followed by BalTS. After the thrombin- treatment, the recombinant BalTS proteins (wild-type and mutants) possess three amino-acids, GSH, at their N- terminals. An E. coli strain BL21(DE3)pLysS was transformed by the expression vectors. The transformants were cultivated in Luria-Bertani medium with 50 μg/mL ampicillin. When the optical cell density of the culture reached 0.5-0.7, the culture was incubated at 15 °C for 30 min without flask-shaking. After the incubation, isopropyl 1- thio-D-galactopyranoside (IPTG, final concentration 1 mM) was added to the medium and cultured at 15 °C for an additional 24 h. The cells were harvested by centrifugation. The harvested cells were resuspended in flow buffer composed of 20 mM Tris-HCl (pH 8.0), 300 mM sodium chloride and 5 mM dithiothreitol. The suspension was sonicated and centrifuged (30,000 g for 1 h at 4 °C), and the supernatant was applied to a Ni-NTA superflow (QIAGEN) column equilibrated with the flow buffer. The column was washed with binding buffer (flow buffer supplemented with 10 mM imidazole) and wash buffer (flow buffer supplemented with 30 mM imidazole). The bound BalTS was eluted with elution buffer (flow buffer supplemented with 250 mM imidazole). The eluent was used for enzymatic assays, or applied to a Superdex200 increase 10/300 column (GE Healthcare) for further purification for crystallization. The column was equilibrated with a gel filtration buffer composed of 25 mM Tris-HCl (pH 8.0), 25 mM ammonium chloride, 1 mM magnesium chloride, 300 mM sodium chloride and 5 mM dithiothreitol at a flow rate of 0.5 mL/min at 4 °C. Thrombin (GE Healthcare) was added to the fractionized BalTS (10 units thrombin per 1 mg BalTS) and incubated 1 day at 4 °C. The sample was concentrated and re-applied to the Superdex200 increase 10/300 column (GE Healthcare) for the final purification. The protein purity was judged by SDS-PAGE, and the concentration was determined by UV- absorption at 280 nm (1.42 for 1 mg/ml BalTS). The selenomethionine (Se-Met) derivative of BalTS was prepared as follows. E. coli B834(DE3)pLysS cells were transformed by the BalTS expression vector. The cells were cultivated in a Se-Met medium composed of 1 g/L ammonium chloride, 4.5 g/L potassium dihydrogenphosphate, 10.5 g/L dibasic potassium phosphate, 0.5 g/L trisodium citrate, 0.2 g/L magnesium sulfate, 10 g/L D-(+)-glucose, 7 mg/L iron(III) chloride hexahydrate, 0.5 g/L thiamine, 0.5 g/L biotin, 19 kinds of amino acids not including methionine (80 mg/mL each), 4 kinds of nucleotide base (adenine, guanine, thymine and uracil, 0.5 g/L each), and 50 mg/mL selenomethionine. Induction by IPTG, cell harvest and purification were performed as non-derivatized BalTS.

Crystallization and crystallographic analysis of BalTS Both the native and the selenomethionine derivative of the purified BalTS were concentrated to 11 mg/mL. Crystallization was performed with the hanging-drop vapor-diffusion method. The BalTS samples were mixed with an equal amount of the precipitant solution and equilibrated with the precipitant solution at 20 °C. The precipitant solution for the native crystals was composed of 15% (w/v) polyetheleneglycol3350 (PEG3350), 0.1 M N,N-Bis(2-hydroxyethyl)glycine (BICINE, pH 9.0), and 200 mM ammonium phosphate dibasic, whereas that for the selenomethionine derivative crystals was composed of 16% (w/v) PEG3350, 0.1M BICINE (pH 8.5), and 200 mM ammonium phosphate dibasic. The crystals were dipped in the cryoprotectant solution for several seconds and flash-frozen in a dry nitrogen- stream at 100 K. The components of the cryoprotectant solution for native crystals were 25% (w/v) PEG3350, 0.1M BICINE (pH 9.0), 200 mM ammonium phosphate dibasic, and 10% (v/v) glycerol, whereas those for selenomethionine derivative crystals were 32.5% (w/v) PEG3350, 0.1 M BICINE (pH 8.5), and 50 mM ammonium phosphate dibasic. The data sets were collected on beamline 5A (Se-Met dataset) and beamline NE-3A (Native) at the Photon Factory, KEK, Japan, using X-ray wavelengths of 0.9788 Å and 1.000 Å, respectively. The datasets

S3 were processed with the program XDS.1 Phasing was performed with the single-anomalous-dispersion (SAD) method using the program SOLVE.2 The initial model was automatically constructed by the program RESOLVE3 with the selenomethionine derivative dataset. Then, the model was manually modified using the program COOT4 5 and refined using the program REFMAC with the native dataset. The model was refined to R and Rfree factors of 0.204 and 0.229, respectively, with the translation-libration-screw (TLS) technique. The data and the refinement statistics are shown in Table S1. The Protein Data Bank (PDB) ID for the refined model is 5YO8.

Oligomeric state analysis The molecular weight of BalTS in solution was analyzed using a size exclusion column Superdex 200 increase 10/300. The column was equilibrated with gel filtration buffer prior to the analysis. The purified BalTS (2.9 mg/mL) was applied to the column at a flow rate of 0.55 mL/min. The retention volume was compared with that of the marker proteins applied to the same column under the same conditions. The markers used were 1.0 mg/mL blue dextran (2 MDa), 0.8 mg/mL ferritin (440 kDa), 5.4 mg/mL aldolase (158 kDa), 3.0 mg/mL conalbumin (75 kDa), 3.8 mg/mL ovalbumin (43 kDa), 2.6 mg/mL carbonic anhydrase (29 kDa), 3.2 mg/mL ribonuclease A (13.7 kDa), and 2.6 mg/mL aprotinin (6.5 kDa). All of the markers were purchased from GE Healthcare Science.

Analysis of the dimer geometry The oligomer states of determined terpene synthases in protein data bank (PDB) were estimated by PISA.6 One subunit of each dimeric enzyme was superposed on a subunit of BalTS. The superposed subunits are shown in white in Fig. 2c, and the other monomers are represented in various colors. The superpoed enzymes are selinadiene synthase from S. pristinaespiralis (PDB 4OKM, cyan for the non-superposed subunit),7 2- methylisoborneol synthase from Streptomyces coelicolor (PDB 3V1X, red),8 MoeN5 from Streptomyces ghanaensis (PDB 5B00, yellow),9 geosmin synthase from Streptomyces coelicolor (PDB 5DZ2, orange),10 germacradien-4-ol synthase from Streptomyces citricolor (PDB 5I1U, yellow-orange),11 (+)-bornyl diphosphate synthase from Salvia officinalis (sage) (PDB 1N1B, magenta),12 γ-terpinene synthase from Thymus vulgaris (PDB 5C05, bright yellow-green),13 pentalenene synthase from Streptomyces exfoliates (PDB 1HM4, pink),14 ent-kaur- 16-ene synthase from Bradyrhizobium japonicum (PDB 4XLX, light blue),15 aristolochene synthase from Penicillium roqueforti (PDB 1DGP, pale cyan),16 cyclooctat-9-en-7-ol synthase from Streptomyces melanosporofaciens (PDB 4OMG, brown),17 and trichodiene synthase from Fusarium sporotrichioides (PDB 1JFA, blue-purple).18

Vector construction, expression and purification of BsuTS The BsuTS gene was initially inserted into pCold I vector by the same strategy to construct pColdTF-ytpB, which was used for our previous investigation.19 These vectors were named pColdI-BsuTS-standard and renamed pColdTF-BsuTS-standard (TF+standard in Fig. S6b), respectively. The BsuTS gene on the two BsuTS-standard vectors contains the L258S replacement comparing to the database sequence (Kyoto Encyclopedia of Genes and Genomes (KEGG) entry ID: BSU30500). Also, the gene contains one NdeI digestion site (81st to 86th bases). The NdeI site in the BsuTS gene in pColdI-BsuTS-standard plasmid was removed by inverse PCR method using primers BsuTS-delNdeI-F and BsuTS-delNdeI-R (5’-TGGACATTTGGAAGCAAAAATCAGAATCGATTC-3’ and 5’- GCTTCCAAATGTCCAGCTCCTGATGAACGAGCG-3’). The resulting plasmid pColdI-BsuTS-delNdeI was amplified using primers BsuTS-pCold2-F and BsuTS-pCold2-R (5’- CCAATTCATATGAGCAGTGGTCTGGTGCCGCGTGGTAGCCACTTGACAGTACCGGAACATCCTTTT-3’ and 5’- CCAATTGGATCCTCAGCAAATGATTTGAGCTTTTTTCTT-3’; NdeI and BamHI sites are underlined). The amplified DNA fragment was digested by NdeI and BamHI and inserted into pCold II vector. The resulting plasmid pColdII- BsuTS-standard (standard(control) in Fig. S6b) expresses TEE-tag, His6-tag and thrombin digestion sites at their N-terminal as BalTS. Also, the BsuTS coding region on pColdII-BsuTS-standard does not contain NdeI digestion site. The L258S replacement in pColdTF-BsuTS-standard and pColdII-BsuTS-standard vectors were removed by inverse PCR method using primers BsuTS-S258L-F and BsuTS-S258L-R (5’-GAGGACTTGCTGGAAGGAGACTTGAA-3’ and 5’- TTCCAGCAAGTCCTCCTCTTGATCAA -3’). The resultant plasmids were named pColdTF-BsuTS-database and pColdII-BsuTS-database (TF+database and database in Fig. S6b), respectively. C-terminal truncation mutants were constructed by inverse PCR method using pColdII-BsuTS-standard as the template. The K349ter, F350ter, Q351ter, K352ter, and M353ter mutants, whose C-terminal residues are K349, F350, Q351, K352, and M353, are constructed using the primer pairs of K349ter-F/K349ter-R (5’- CGGAAATGATTTCAAAAAATGTCCTGG-3’/5’-TTGAAATCATTTCCGGTAGGCTCTGCC-3’), F350ter-F/F350ter-R (5’- AAATTTTGACAAAAAATGTCCTGG-3’/5’-TTTTTGTCAAAATTTCCGGTAGGCTCTGCCGTT-3’), Q351ter-F/Q351ter-R (5’-TTTCAATGAAAAATGTCCTGGATG-3’/5’-CATTTTTCATTGAAATTTCCGGTAGGCTCTGCC-3’), K352ter-F/K352ter-R (5’-CAAAAATGAATGTCCTGGATGTCC-3’/5’-GGACATTCATTTTTGAAATTTCCGGTAGGCTCT-3’), and M353ter- F/M353ter-R (5’-AAAATGTGATCCTGGATGAAAAATTCA-3’/5’- CCAGGATCACATTTTTTGAAATTTCCG-3’), respectively. The sequences of the all plasmids were confirmed by DNA sequencing (Hokkaido System Science Co., Ltd., Sapporo, Japan or Macrogen Japan Corp., Kyoto, Japan).

S4 An E. coli strain Novablue was transformed by the vectors, and cultivated in Luria-Bertani medium with 50 μg/mL ampicillin. Induction of BsuTS overexpression and harvesting of the cells were performed as BalTS. Resuspension and sonication of the harvested cells, and purification using the Ni-NTA resin of BsuTS were also performed as for BalTS. The eluent from Ni-NTA resin with elution buffer was dialyzed against the gel filtration buffer overnight at 4 °C. The samples were concentrated to the appropriate concentration and used for the enzymatic assays.

Homology modeling of BsuTS Homology model of BsuTS was constructed using swiss-model20 server using the refined crystal structure of BalTS as a template. The BsuTS model structure was constructed as a monomer. The monomeric model was dimerized based on the dimeric assembly of BalTS. It should be noted that no information is available to date regarding the oligomeric state of BsuTS.

Enzymatic assays The substrates (1-4) for the enzymatic assays of BalTS and BsuTS were prepared as previously described.21, 22 For the product analysis (shown in Figs. 1 and 4), the reaction mixture was composed of 25 mM Tris-HCl buffer (pH 8.5), 10 mM dithiothreitol, 1 mM MgCl2, 130 µM substrate (1-4), and 0.93 µM purified enzyme (BalTS or BsuTS) in a total volume of 2 mL. The reaction was carried out at 37 C for 16 h. A 15% KOH/MeOH solution (3 mL) was added to terminate the reaction. The lipophilic product was extracted from the reaction mixture by using n-hexane (3 × 5 mL) and analyzed by GC-MS (injection temperature, 300 C; oven temperature, 60–280 C in increments of 10 C min-1). The products were identified both by comparisons of the GC-MS spectrum and by co-injection experiments with authentic prenes 6-9. The authentic 7-9 were isolated in previous studies 21, 22, and 6 was obtained and analyzed in this study (Figs. S7-S11). The GC-MS analysis of n-hexane extracts from B. alcalophilus cells was also performed under the same conditions. For the activity measurements of BalTS (Fig. 3c), reactions were performed with substrate 1 in the same manner as for the product analysis, except that the incubation time was 1 h. The amount of product was quantified with GC (injection temperature, 300 C; oven temperature, 220–300 C in increments of 3 C min-1).

Isolation and identification of β-springen (6) The reaction mixture contained 25 mM Tris-HCl buffer (pH 8.5), 10 mM dithiothreitol, 1 mM MgCl2, 130 µM (11.7 mg) 1, and 7.5 µM purified BalTS in a total volume of 200 mL. The reaction was carried out at 37C for 16 h. After 15% KOH/MeOH solution (240 mL) was added to the reaction mixture, the lipophilic products were extracted with n-hexane (440 mL × 3) and concentrated. The n-hexane extract (28.6 mg) was partially purified by silica gel (3 g) column chromatography with n-hexane and n-hexane/EtOAc (100:20). The fraction (3.4 mg) eluted with n-hexane containing the product 6 was subjected to SiO2 HPLC (Inertsil PREP-SIL, 6.0 × 250 mm; GL Science) with n-hexane, and pure 6 (colorless oil; 1.8 mg) was obtained. The structure of 6 was determined to be β- + springene by MS (Fig. S7) and NMR (Figs. S8-S11). HR-EI-MS: m/z calculated for C20H32 [M] 272.2504; found 272.2509.

S5 Movie Captions Movie S1. Surface representation of the physiological dimer of BalTS. White and gray molecules indicate the respective monomers. Carbons, nitrogens, and oxygens of highly conserved residues in homologue proteins are colored green, blue, and red, respectively.

Movie S2. Surface representation of BalTS. The six characteristic aspartates and hydrophobic residues conserved in homologous enzymes are colored in magenta and yellow, respectively.

Movie S3. Surface representation of BalTS showing distribution of conserved residues between BalTS and BsuTS. Yellow and green parts represent identical and similar residues shown in Fig. S5, respectively. Brighter and darker colors represent each subunit of BalTS. The BalTS molecules in Movies S1-S3 are rotated around the same axis. Only the color scheme is different from each other.

Author Contributions M.F. and T.Sa designed the whole project, analyzed the results. M.F. and Y.T. determined the crystal structure of BalTS. D.Y., T.N., D.U and M.M. analyzed the reactions of BalTS and BsuTS. Y.Y., A.S., K.F., and T.Sh synthesized the substrates of BalTS and BsuTS. K.M. administrated and supervised the project. The manuscript was written by M.F. and T.Sa, edited by T.Sh and K.M., and approved by all authors.

S6 1------MK V P T QP I P L MMN I F RD V L P T V HR Y ------Y DQ K-30

1- mh k f t g v n a k f qq p a l RN L SPVVV E R E RE - E F VGF F P Q I V RD L T E DG I GHPE V GDA V AR L -59

1------mp QD V D F H I P L PGRQS P DHAR A E A EQ ------L A P R-31

31- E - - RA KS I P D P E L RAQA L DA L E RK E F HCE GG G I Y - GL L A ------RD R F DE L I -74

60- K - - E V ------L QY NA PGGKC - NRGL T V V AA Y R E L S GP GQKD A E S L RC A L A V G-103

32- S L GL I RS ------DAA A E RH L RG - GY AD L AS R F - Y P HA ------T GAD L -66

75- QF I I A YQ I MCD Y L DN L CDQS DY L D P KD F RS L HN - A L L AA L T PGE P L V N Y YQY R I EQE DGG-133

104- C I E L F QA FF L V ADD I MDQS ------L T RRGQL C Y KK E GVGL DA I N-144

67- D L GV D L MS FFL F DD L F DGP RGE N P E D T KQL T DQV AA A -- - L DGP L P D ------T A P -114

134- Y L H E L I E T CQH I L V T --- - F P S F RMVQENML E L SQL Y GD L QV HK H V - - V KE E - R I P R L E A -186

145- D S FL L ESSV Y R V L KK Y CRQR PYY V H L L E LF L QT A YQT E L GQML D L I T A PV S K V D L S H F S - -203

115- P I AHGF AD I RR T CE --- - GMT - P A CA R S AR H RN Y F DGY V D E A E SR f wn a p c d ------164

187- F N E HKE KMP EMT F E F S AC - T GS T - - L GV Y T L A T Y A - T K EGL T S E QAD - - V I KAGY F P -240

204------E E R Y KA I V KY K T A F Y S F Y L P V AA AMY - MVG I DS K E E H E - - NAK A I L L - E -248

165------S AAQY L AMRR - H T I G - - V QP T V D L AE RAGR F EV P HR V F DS A VMS AML Q - I -210

241- V QGV H LL L D Y F I DQ ------E E D I AD D E L N F L - F YY E ------270

249- MGE Y F Q I QDD Y L DC F GD P A L T GK V GT D I - QDNK C S L V VQC L QR V T P E QRQL L EDN Y GRK-307

211- A V D V N LL L ND I A S L ------E K E E ARGEQNNMVM I L R ------241

271------N E EQM I E R F QY F V QKA EE S L - S ------291

308- E P E K V AK V K E L Y EA V GMRA A F QQY EE S S Y RR L QE L I E K ------345

242------RE HG S K S R SV SHMQN E V RA R L EQY - LL L E S C L PK V GE I YQL D T A E R E A-289

292- T L P - - DP K F - HR H I RG I I A I Y L S D E K VQKN K E L KK KS KQM I KMGGL P S LL F Y L N S I Y R-348

346- H S NR L PK E I - F L GL AQK I Y ------KRQK -367

290- L E R - - Y R T DA V R T V I RGS Y D HRS ------S -312

349- R d k -351

313- G r y -315

Fig. S1. Structural sequence alignment amongSup pBalTS,orting farnesyl Figure Sdiphosphate1 synthase from avian (AvFPPs, a prenyltransferase),23 pentalenene synthase from Streptomyces exfoliates (SePENTs, a Class I terpene synthase).24 Cartoon over the sequences show helix names for each structure. Small red and blue closed circles represent the helix kink on BalTS and SePENTs, respectively. Residues (potentially) involved in the binding of pyrophosphate part of the ligands are highlighted in red font with yellow background.

S7 Class I enzymes Class IB enzymes (large terpene synthase) prenyl-pyrophosphates

C5 (rare) OPP C10 (major) OPP Substrates C15 (major) OPP C20 (major) OPP C20 OPP (non-natural substrate) C25 (rare) OPP C25 OPP C30 OPP C35 OPP

large Cleft size shallow penetrating hole Primary structure no similarity categolized in the same group

3D structure

NSE/DTE YL NLx Motif sequence D D D DDxxD DY(F,L,W)IDxxED

leaving pyrophosphate from the substrate

Reaction trigger OP2O6 n

+ Various Products n

Fig. S2. Summary of the differences between Class I and Class IB enzymes.

S8 Kav 0.6 0

8 y=0-.31x+1.90 2 0.4

A R² =0.996 0.2 0.0 4 5 6 log10Mw

6 8 10 12 14 16 18 20 ml

Fig. S3. Oligomer state analysis of BalTS by size-exclusion chromatography. Gray lines represent the peaks for marker proteins, whereas thick black line shows that for BalTS. The estimated molecular size of BalTS is 89,000 Da, which is very close to twice the calculated molecular size of a BalTS subunit (43,189 Da). The estimated oligomeric state suggests that the two subunit in an asymmetric unit of the crystal is the physiological dimer.

S9 1 1 0 BalTS ...... M K V P T Q P IP L M dor ...... M N T L D I G P A N N VK L I dmi ...... M N R S S L R T Y N S IK L I dai ...... M K V V K K G S I N R GK L I ddh ...... M D I A K E V S N PQ L I dsy ...... M D I A K E V S K PQ L I ddl ...... M E I A K Q V S N PR L I puf ...... M N T F L N P F G N LT L I pft ...... M K F F A K F Y K V LS L I gfe ...... M D Q SK I I toc ...... M K E C F Y R FS L L mas ...... M R V L Q R N P G W Q Y E K K G I A P K G R A F S R R L G D G I L A P G E F L Y K SR K I tpz ...... M A S D R H R R S S L A E E A K K IA L L dau ...... M P G G V G V S V A R K L P A Q MA F I mta ...... M A A A G I R P LV T L dku ...... M F T C W E S K P C P G K W E V A A R LG L M slp ...... M R C L P P AS W L swo ...... M P G L A N R T Q E S K L A L L M Q H G L R G G R MN L L blr ...... M Q A K P I H K P WQ L L bbe ...... M S E L R N P WQ L L pnp ...... M pms ...... M plv ...... M K R P N N Q A A Q V P R N P LR L M pow ...... M D D T G G R F S L R V P Q E P LL L M pbj ...... M E G A F L R E Q G L K A G R V P R G P IL L M pjd ...... M R V M T L S G N R V P E R P LK L M pdu ...... M S E F Q Q G R S L S P R G P IG L M psab ...... M S E F E Q G R S L S P R G P IG L M pste ...... M S E F E Q G R P S S P R G P IG L M paee ...... M N E F E Q G R Y L S P R G P IG L M paea ...... M N E F E Q G R Y L S P R G P IG L M paeq ...... M N E F E Q G R Y L S P R G P IG L M paen ...... M N E F E Q G R Y L S P R G P IG L M pbd ...... M K E F E Q G R Y L S P R G P IG L M paeh ...... M S E F E Q G R Y L S P R G P IG L M pgm ...... M N E F E Q G R Y L S P R G P IG L M pri ...... M E A L S L N E F E Q G R Y L S P R G P IG L M paej ...... M S E L E Q G R Y L S P R G P IG L M paef ...... M S E L E Q G R N L S P R G P IG L M pod ...... M S E L E Q G R Y L S P R G P LG L M gym ...... M N N Q E L S R K V P R S P VG L M ppeo ...... M S Y V E Q G R Y Q V P R G P IG L M ppy ...... M S Y V E Q G R Y Q V P R G P IG L M pta ...... M S Y V E Q G R Y Q V P R G P IG L M pih ...... M K Y N E K S Q Y Q V P R N P LN L M pbv ...... M N D M M Q S R Y P F P R N A IS L M tco ...... M N A T R K H G S G M P A G P LR L M anx ...... M I L V K V V L N G L Y P R G P LR L M bpf ...... M K V P T K P IP I L bha ...... M S A P T W P LP L L bcl ...... M G T V P A N P FK I I ble ...... M Q S V P T N A IK V V bmet ...... M F I P S E P IS L M gst ...... M M P IT L M baci ...... M E S Y Y P L K R D K R G V E M T I P T Q P IS L M bif ...... M T V P S M P IP L M bsm ...... M T I P T H P FS L M bck ...... M jeo ...... M A V P N E P LF L M bmq ...... M K I P S H P IS L M beo ...... M E I P K H P FM L M bacy ...... M T V P E H P FG L M bsus ...... M T V P E H P FG L M balm ...... M L T V P E H P FG L M bjs ...... M bacl ...... M L T V P E H P FG L M bae ...... M T V P E H P FG L M bacp ...... M T V P E H P FN L M bacb ...... M T V P E H P FN L M bay ...... M L T V P E H P FN L M bao ...... M T V P E H P FN L M bli ...... M A V P E H P FG L M blh ...... M A V P E H P FG L M bgy ...... M S V P E H P LG L M bacw ...... M S V P E R P FA L M bpu ...... M S V P E R P FA L M gth ...... M K I P T H P IT L M gmc ...... M K I P T H P IT L M gwc ...... M K I P T H P IT L M gtn ...... M K I P T H P IA L M gsr ...... M K I P T H P IA L M gjf ...... M K A S F L R P E V S K L K I P T H P IA L M gse ...... M V F A P E V S R L N I P K N P IA L M gct ...... M V F A P E V S R L N I P K N P IA L M gya ...... M V F A P E V S R L N I P K N P IA L M gyc ...... M V F A P E V S R L N I P K N P IA L M gte ...... M V F A P E V S R L N I P K N P IA L M gka M V K N V S F R P M S G W D R G R R S D F T K L L N V R R T V V E R L F H S V A N P F M V C P G R I D G N T G R R D R K L F R R E T I L V A D K M E M L G D E T M V F A P E V S R L N I P K N P IA L M ggh ...... M V F A P E V S R L N I P K N P IA L M gej ...... M N I P K N P IA L M gel ...... M V F A P E V N R L N I P K N P IA L M gea ...... M K I P T H P IA L M anl ...... M S L L S I P K H P VS L M anm ...... M S L L S I P K H P VS L M aamy ...... M L S I P T H P VS L M afl ...... M N S L N V P T N P FS L M agn ...... M S V P T N P FS L M bby ...... M N V P S N P IT L M bce ...... M N V P S N P IT L M ban ...... M N V P S N P IT L M btk ...... M K E E V N V P S N P IT L M bty ...... M bwe ...... M N V P S N P IT L M bmyc ...... M N V P S N P IT L M bcy ...... M N V P S N P IT L M far ...... M N K V P V H P WG L M fpn ...... M N K V P V H P WG L M sat ...... M K V P T H L ST L T len ...... M N I P V S P WS L M glj ...... M D I P D S P WA F L npu ...... M L M F R N K Y H N F N K N I K D N L Q K S L L L Q V P S N S GM L M bco ...... M K I P T S S WT L M bse ...... M K T P A L P CQ L M axl ...... M N E R D Y R S A TQ L A tap ...... M A Q Q I P K S S VL L M hhd ...... M T A Q V P Q N A VH L M vig ...... M L S N L V P S T P IP L M lao ...... M sje ...... M tur ...... M F Y PA L M say ...... M A P W T T S WR W V tmr . . . . . M N L A E N G E P F H R D E P G P A A R P L E A A A P R D F F P A G H V R R V N P F R R E P G P S R D A D S P A A R R R S A S A C E A G G V P D V G E P A R S K P P G G A R R L L A E AA R L lpil ...... M R P L A G G G P D A G E IR L L aac ...... M P N G S K L S H SQ F L nth ...... M Q FK S L ctx ...... M I T R C C H G PR L V clb ...... M R N I I G S MR F I Fig. S4. (1/6)

S10 2 5 8 9 8 8 D D D 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 BalTS M N I F R D V L P T V H R Y Y D Q W K E R A K S I P D P E L R A Q A L D A L E R K E F H C E G G G I Y G L L A R D R F D E . L I Q F I I A Y Q I M C D Y L D N L C D Q S D . . . Y L D P K D F R SL H N dor Y R F V T K V F P I V K E E L E R W K Q Q A R Q A P D A R L S Q Q A L E S I R L K A F H C Q G G S I Y A L Y P G I D R L E . T I R F I V A Y Q T M S D Y L D N L V D S M E . . . V Q D E K A F F QL H L dmi Y L F V A K V F P I V K R E L N E W R Q K A R E A P D A R L C Q Q A L E S I R W K A F H C Q G G S I Y A L Y P G V P R V A . T I R F I V A Y Q T M S D Y L D N L V D S L E . . . V Q D E K A F A QL H L dai Y N F V T K V F P M V K E E L M L W R K R A E E I P D S R L S S Q A L E S I R L K A F H C Q G G S I Y A L Y P G A N Q I E . T V R F I V A Y Q T M S D Y L D N L V D N L E . . . I E D E M A F A QL H L ddh Y S F V R T I F P E V K A Q L S F W E Q K A G R C P D R V L R D Q A L S S I A H K E F H C L G G S I Y S L Y P G V R I S E . V I E F V V A Y Q T I S D Y L D N L V D A L E . . . I Q D E Q A F R QL H L dsy Y S F V K T I F P A V K A Q L S F W E E K A G R C P D R V L G E Q A L A S I A H K E F H C L G G S I Y S L Y P G A R V A E . V I E F V V A Y Q T I S D Y L D N L V D A L E . . . I Q D E Q A F R QL H L ddl Y S F I R T V F P E V K S Q L Q D W E H R A S H C P D Q V L A D Q A I A S I R H K E F H C L G G S I Y A L Y P G V R T K E . V I E F V V A Y Q T I S D Y L D N L V D A L E . . . I H D E L A Y G QL H L puf F T F V S K V F P L I T K E L T H W S N Y A S S H A S S E L R T Q A L A S I R D K K F H C Q G G S I Y S L Y P T V D I A T . F I P L I V S L Q T I S D Y L D N L C D R A D . . . I M D E Q A F K QL H L pft I P F V R K V F P L V D S E L H H W S T K G I S H A C P E L K E Q A L A S I A N K K F H C Q G G S I Y S L Y P T V C K T D . F I S L V V A L Q T I S D Y L D N L C D N A G . . . I T D E Q A F R QL H Y gfe Y T F V K D V F P V V K K E L H F W Q Q K A A E A S S N I L S E Q A S A S I G K K S F H A Q G G S I Y S L Y G S S M D E N . L I K F I V A L Q T I S D Y L D N L C D R V G . . . V E D V N A F L QL H C toc Y K F V N R I F P L V D A E L K K Y T T L A E R I P D P V L S H Q A L E S I K E K K F H C Q G G S V Y A L Y P G V S Q K D . M V H F I V S Y Q T I S D Y L D N L C D R A G . . . V M E E K A F R QL H L mas Y D F I F N V F P L V D K Q L E V Y A G I A R H I P D K M L S K Q A L D S I A T K K F H C Q G G S I Y A L Y P H T D G D K . M I K F I V A Y Q T I S D Y L D N L C D R S G . . . I F D E T A F R NL H L tpz T R F V T R V F P G V E R E L G R W R R F L D R A G D E E L R S Q G L A S I E K K K F H C L G G A V Y A L M E G . . A H R D T L R F I V A F Q T I S D Y L D N L C D R T G . . . C L E A A A F R RL H R dau G R F L T L V L P D V D R E L A R W Q A K I S E C P E S E L A R Q A A S S I R L K R F H A Q G G S V F A L T A G G . Y R R D L V R L I V A L Q T I S D Y L D N L C D R A G . . . C Y D R H A F R ML H E mta G Y F L F Q G F P G V N R E L A G W R R R A A A I P D P R L R E Q A L A S L T L K K F H C Q G G S V Y A A W P R R . H C R E L L R A I V A L Q T I S D Y L D N L C D R A G . . . I L D E E A F R QL H L dku G R F L F L A F P G V A R E L K N W R L M A S R C P E P H L R R M A L A S I G A K A F H C Q G G S V F S A W T G S . Y R R E L I R A I V A L Q T I S D Y L D N L C D R A G . . . V Q D G E A F Y RL H R slp C R Y L K E V L P L V D K E L L V W R E K A D N I E D E S L R H Q A L D S L E A K A F H C Y G G A V M S L L G P K E R L E D L V A L I V A F Q T I S D Y L D N L C D R A G . . . I V D E V A F T RL H Q swo S H Y I L F T L S Q V K S Q L K V W E Q E A R L C P N E E L R K Q A L S S I H N K G F H C Q G G A F F A V P Y R E . K E T L L L R L I I A Y Q T L C D Y L D N L C D R T A . . . C S D G K A F R QL H R blr Y R V Y R Y I L P L L E Q E F A Y W Y E R A K E I P D R E L R K Q A I A S M D T K K F H C Q G G S V Y A S Q V M A Y K E T . L V K L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P I D F R QL H Y bbe Y R V Y R H V Q P V L E R E F A A W Y K R A Q A I P N P E L R K Q A Q D S M D S K K F H C Q G G C V Y A A Q V I P H V E T . I V P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P Q D F R QL H V pnp L R V Y R H V L P A V R E Q L D H W R S K A E Q I P D A E L R K Q A I N S L T S K Q F H C E G G A V Y A A A N L S M R H I . L I P L I A A F Q T I S D Y L D N L C D R S T . . . S L D P E D F R RL H Q pms L R V Y R Y V L P G V R E Q L K H W R T R A Q A I P D A E L R R Q A L A S M A C K Q F H C E G G A V Y A V A N M S M R H V . L I P L I V A L Q T I S D Y L D N L C D R S T . . . S L D P E D F R QL H Q plv F R V Y R Y V L P T V D K E L R R W T S K V E Q I P D P E L K Q Q A L A S I T A K R F H C Q G G A V Y G I V H L S E H H R . L I P L I V A F Q T I S D Y L D N L C D R S T . . . S L D P A D F R ML H Q pow Y R V Y K Y V L P D V S A E L A K L R S A A E R I P D A E L R A Q A L A S M E A K R F H C Q G G A V Y A A A D P D M R H V . L I P L I V A L Q T I S D Y L D N L C D R S T . . . S L D P D D F R LL H R pbj Y R V Y K Y V L P D V A V Q M D A L R E R A S R I P D A E L R T Q A L N S M T E K K F H C Q G G A V Y A A A S L Q Y R D V . L I P L I V A L Q T I S D Y L D N L C D R S T . . . S L D E E D F R LL H Q pjd H R V Y K Y I L P E V N I E L R K L R R L A E Q I P D P E L R L Q A L Q S M D S K K F H C Q G G A I Y A S M N L D E R Y V . L I P L I V A L Q T I S D Y L D N L C D R S T . . . S L D P D D F R LL H Q pdu S R V Y K Y V L P E V R N C L N H W R K D A E G I P D P E L R K Q A L A S I E T K Q F H C E G G G V Y A A G N L P M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S M D P A D F R LL H Q psab S R V Y K Y V L P E V R N C L N V W R K D A E G I P D P E L R K Q A L A S I E T K Q F H C E G G G V Y A A G N L P M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S M N A E D F R LL H Q pste S R V Y K Y V L P E V E N C L N L W R K D A E G I P D P E L R R Q A L A S I E T K K F H C Q G G G V Y A V G N L P M R H I . L I S L I V S Y Q T I S D Y L D N L C D R S T . . . S M D P E D F R LL H R paee S R V Y K Y V L P E V R E C L H A W R Q D A E G I P D P E L R K Q A L A S I E T K Q F H C E G G G I Y A A G N L S M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P A D F R LL H Q paea S R V Y K Y V L P E V R E C L H S W R Q D A E G I P D P E L R K Q A L A S I E T K Q F H C E G G G I Y A A G N L S M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P A D F R LL H Q paeq N R V Y K Y V L P E V R A C L D F W R Q D A E G I P D P E L R K Q A L A S I E T K Q F H C E G G G I Y A A G N L S M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P A D F R LL H Q paen N R V Y K Y V L P E V R A C L D F W R Q D A E G I P D P E L R K Q A L A S I E T K Q F H C E G G G I Y A A G N L S M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P A D F R LL H Q pbd N R V Y K Y V L P E V R A S L D F W R Q D A E G I P D P E L R K Q A L A S I E T K Q F H C E G G G I Y A A G N L S M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P A D F R LL H Q paeh N R V Y K Y V L P E V R E C L G F W R Q D A E G I P D P E L R K Q A L A S I E T K Q F H C E G G G I Y A A G N L S M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P A D F R LL H Q pgm S R V Y K Y V L P E V R E C L H F W R Q D A E G I P D P E L R K Q A L A S I E T K E F H C Q G G G I Y A A G N L S M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P D D F R LL H Q pri S R V Y K Y V L P E V R E C L H F W R Q D A E G I P D P E L R K Q A L A S I E T K E F H C Q G G G I Y A A G N L S M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P A D F R LL H Q paej N R V Y K Y V L P E V R E S L D F W R Q D A N G I P D P E L R K Q A L A S I E T K E F H C I G G G I Y A A G N L S M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P A D F R LL H Q paef N R V Y K Y V L P E V R E C L H F W R Q D A N G I P D P E L R K Q A L A S I E T K E F H C I G G G I Y A A G N L S M R H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P A D F R LL H Q pod N R V Y K Y V L P E V R E C L H F W R Q D A N G I P D P E L R K Q A L A S I E T K E F H C I G G G I Y A A G N L S M K H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P A D F R LL H Q gym S R V Y K F I L P E V R S E L E K W R R E A E Q I P D E E L R K Q A L A S I D T K R F H C Q G G A V Y A A A N L P E K H I . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S L D P A D F R QL H Q ppeo S R M Y K H I L P E T K L E L S N W K S K A E Q I P D P E L R S Q A L A S I A D K T F H C V G G A V Y A A A N M S A R Q T . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S M D P D D F R LL H Q ppy S R M Y K H I L P E T K L E L S N W K S K A E Q I P D P E L R S Q A L A S I A D K T F H C V G G A V Y A A A N M S A R Q T . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S M D P D D F R LL H Q pta S R M Y K H I L P E T K Q E L G N W K H K A E Q I P D P E L R S Q A L A S I A E K T F H C V G G A V Y A A G N M S A R Q T . L I P L I V A Y Q T I S D Y L D N L C D R S T . . . S M D P D D F R LL H Q pih S R V Y K H I L P E V R K E L D G W R K V A G E I P D L E L R K Q A L D S L E T K Q F H C Q G G A V Y A A I E L P E R H T . L I K L I V A Y Q T I S D Y L D N L C D R S T . . . S M D P E D F R LL H Q pbv Q R V Y K Y G L P E V R Q E L D V W R S M A E R M P D E E L R K Q A L A S I A T K Q F H C E G G A I Y A V A N I S Q R H I . L L P L I V A F Q T I S D Y L D N L C D R S T . . . S M D P D D F R LL H Q tco Y R M Y R H V L P A V Y D E L A R W R A R A E A I P D P E L R T Q A L A S M S S K Q F H C E G G A V F A A A V N D R H G E . L V P L I V A L Q T I S D Y L D N L C D R S T . . . S L D P D D F R LL H R anx Y R L Y R H I F P A V R A E V E R W R E R A G Q I P D P E L R K Q A L D S I E N K R F H C E G G S V Y A A A H L A W K E P . L I R L I V A Y Q T I S D Y L D N L C D R S T . . . S L G A N N F A RL H Q bpf M N I Y R D V V P T V N R Y F N Q W I E K A Q T I P D D E L R S Q A L D A L S K K K F H C E G G G V F G L V A R D R F D E . L I Q F I I A Y Q I M C D Y L D N L C D Q S D . . . S L D P K D F R AL H N bha K A V Y Q E V L P A V H Q K L E K L K E R A A T I P D E T L R F H A L D A L T R K A F H C E G G G V F G L I E R T C F D E . F L T F L I H Y Q Q M C D Y L D N L C D Q S D . . . S L D P N D F R TL H N bcl Q L A F K E T V P K A H A E L Q K W H Q E A L K I D D V E I R E Q A A W T V N D K T F H C E G G S I F A L L A G E N K D N . H I Q F L V A Y Q T I C D Y L D T L C D K N D . . . A H D P N D F R SI H Q ble S R A K K E T I P Q A H E E L R H W K S E A M K I Q D E S I R E Q A A W T V S D K T F H A E G G S I I G L L S G A N K D R . Y I Q F M V G Y Q S I C D F L D T L C D K N D . . . S T N P D D F R SI H N bmet A K V Y R K I L P E V H R E L E Y W K K R A E E I P D P E L R K Q A L S S I E H K S F H C E G G A I L A L A A N E R Y K E . A I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P C D F A AL H D gst A K V Y R K I L P A V H Q E L A Y W K S R A E N I P N P E L R K Q A L A S I A Q K A F H C E G G A I L A L T A N E H Y Q K . A V K F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P N D F A AL H E baci S S V Y W K V L P T V Q Q E L D Y W K K K A E A I P N P E L R K Q A I A S I A N K T F H C Q G G S I L A L L A T D K W R Q . A I K F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P V D F A SL H E bif T K V Y K K I I P E V H R E L A Y W R E R A G N I P D P E L R K Q A L A S I G H K A F H C E G G A I M A L L A K D R Y K E . A V R F I V A Y Q T V S D Y L D N L C D R S T . . . S Q D P A D F S AL H E bsm G Q A Y R K V F P T V H K E L N K W K Q K A N S I P D Q E L K K Q A L A S I E H K T F H C E G G S I L A L L S G E H F G E . A V K F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P K D F A AL H E bck A Q V Y R R V M P A V H H E L H Y W R E K A R R I P N D E L K T Q A L A S I Q H K T F H C E G G S I L G L L A M E E R T A . A F R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P V D F R AL H E jeo N Q V Y R K V F P I V H R E L F Y W K Q K A L Q I E N E E L K K Q A I D S I T Y K A F H C E G G G I M S L L A L K G K R D . A I E F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P E D F A AL H Q bmq R K I Y R E V F P V V H H E L N H W R E R A K E I P N K E L R T Q A L A S I D T K T F H C E G G G I L S I L A K E N M I E . C V K F I V A Y Q T I S D Y L D N L C D R S N . . . S L D P K D F A AL H E beo R K V Y K E V M P I V H E E L L K W K K K A R N I P N E E L R T Q A L A S I N D K T F H C E G G S I M G L L A C G E F K K . A I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F A AL H E bacy A K V Y R D I F P L V H Q E L D I W K Q K S E S I H N S E L K A Q A T A S I R D K T F H C E G G G I L A L L S G S Q K Q K . C V E F I I A Y Q T I S D Y L D N L C D R S T . . . S L D P Q D F R ML H A bsus A K V Y R D I F P L V H Q E L D I W K Q K S E S I H N S E L K A Q A T A S I R D K T F H C E G G G I L A L L S G S Q K Q K . C V E F I I A Y Q T I S D Y L D N L C D R S T . . . S L D P Q D F R ML H A balm A K V Y R D I F P L V H Q E L D I W K Q K S E S I H N S E L K A Q A T A S I R D K T F H C E G G G I L A L L S G S Q K Q K . C V E F I I A Y Q T I S D Y L D N L C D R S T . . . S L D P Q D F R ML H A bjs A K V Y R D I F P L V H Q E L D I W K Q K S E S I H N S E L K A Q A T A S I R D K T F H C E G G G I L A L L S G S Q K Q K . C V E F I I A Y Q T I S D Y L D N L C D R S T . . . S L D P Q D F R ML H A bacl A K V Y R D I F P L V H Q E L D I W K Q K S E S I H N S E L K A Q A T A S I R D K T F H C E G G G I L A L L S G S Q K Q K . C V E F I I A Y Q T I S D Y L D N L C D R S T . . . S L D P Q D F R ML H A bae T K V Y R D I F P L V H Q E M K I W Q S K S E S I R N S E L K A Q A M A S I R D K T F H C E G G G I L A L L S G D E K Q K . C V E F I I A Y Q T I S D Y L D N L C D R S T . . . S L D P D D F R ML H A bacp A K V Y R E I F P L V H Q E L N M W R E K S D S I K N T E L R Q Q A A A S I R D K S F H C E G G G I L A L L S G E Q K Q K . C V Q F I I A Y Q T I S D Y L D N L C D R S T . . . S L D P E D F R ML H L bacb A K V Y R E I F P L V H Q E L N M W R E K S D S I K N T E L R Q Q A A A S I R D K S F H C E G G G I L A L L S G E Q K Q K . C V Q F I I A Y Q T I S D Y L D N L C D R S T . . . S L D P E D F R ML H L bay A K V Y R E I F P L V H Q E L N M W R E K S D S I K N T E L R Q Q A A A S I R D K S F H C E G G G I L A L L S G E Q K Q K . C V Q F I I A Y Q T I S D Y L D N L C D R S T . . . S L D P E D F R ML H L bao A K V Y R E I F P L V H Q E L N I W R E K S D S I K N T E L R E Q A A A S I R D K S F H C E G G G I L A L L S G E Q K Q K . C V Q F I I A Y Q T I S D Y L D N L C D R S T . . . S L D P E D F R ML H L bli A K V Y R E V F P L V H Q E L D K W K R K A E T I Q N P E L K T Q A K A S I R D K T F H C E G G G I M A L L S G D K I E Q . S I R F I T A Y Q T I S D Y L D N L C D R S T . . . S L D P D D F T ML H Q blh A K V Y R E V F P L V H Q E L D K W K R K A E T I Q N P E L K T Q A K A S I R D K T F H C E G G G I M A L L S G D K I E Q . S I R F I T A Y Q T I S D Y L D N L C D R S T . . . S L D P D D F S ML H Q bgy A K V Y R E V F P L V H Q E L D K W R T K A E N I E N S E L K M Q A L A S I R Q K T F H C E G G G I L A L L S G E K I R Q . S I R F I T A Y Q T I S D Y L D N L C D R S T . . . S L D P D D F A ML H Q bacw T K V Y K D I F P L V H Q E L K K W R A H A E M I E N E E L R T Q A L A S I S S K T F H C E G G G I L S L L A G E E K E T . C I E F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P K D F H ML H Q bpu T K V Y K D I F P L V H Q E L K K W Q A H A E M I E N E E L R T Q A L A S I S S K T F H C E G G G I L S L L A G D A K E T . C I E F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P K D F H ML H Q gth K K V Y R D V F P V V H R E L A Y W K Q K A Q N I P D A E L R K Q A L A S I E T K T F H C E G G S I L S L L A G E K M E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H E gmc K K V Y R D V F P V V H R E L A Y W K Q K A Q N I P D A E L R K Q A L A S I E T K T F H C E G G S I L S L L A G E K M E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H E gwc K K V Y R D V F P V V H R E L A Y W K Q R A Q N I P E P E L R K Q A L A S I E T K A F H C E G G S I L S L L A G E K M E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H E gtn K M V Y R D V F P L V H R E L S Y W R Q R A E R I P D P E L R R Q A L A S I A S K T F H C E G G A I L A L L A R E K L E A . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D gsr K M V Y R D V F P I V H R E L A Y W Q R Q A E Q I P D P E L R R Q A L A S I A S K T F H C E G G A I L A L L A G E Q L E A . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D gjf K M V Y R D V F P L V H R E L A Y W R R R A E R I P D P E L R R Q A L A S I A S K T F H C E G G A I L A L L S G D K L E A . C V R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D gse K M V Y R D V L P L V H R E L A Y W R R Q A E R I P D P E L R R Q A L A S I A S K T F H C E G G S I L A L L A G E N M E D . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D gct K M V Y R D V L P L V H R E L A Y W R R Q A E R I P D P E L R R Q A L A S I A S K T F H C E G G S I L A L L A G E N M E D . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D gya K M V Y R D V L P L V H R E L A Y W R R Q A E R I P D P E L R R Q A L A S I A S K T F H C E G G S I L A L L A G E N M E D . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D gyc K M V Y R D V L P L V H R E L A Y W R R Q A E R I P D P E L R R Q A L A S I A S K T F H C E G G S I L A L L A G E N M E D . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D gte K M V Y R D V L P L V H R E L A Y W R R Q A E R I P D P E L R R Q A L A S I A S K T F H C E G G S I L A L L A G E N M E D . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D gka K M V Y R D V L P L V H R E L A Y W R R Q A E R I P D P E L R R Q A L A S I A S K T F H C E G G S I L A L L A G E N M E D . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D ggh K M V Y R D V L P L V H R E L A Y W R R Q A E R I P D P E L R R Q A L A S I A S K T F H C E G G S I L A L L A G E N M E D . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D gej K M V Y R D V L P L V H R E L A Y W R R Q A E R I P D P E L R R Q A L A S I A S K T F H C E G G S I L A L L A G E N M E D . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D gel K M V Y R D V L P L V H R E L A Y W R R Q A E R I P D P E L R R Q A L A S I A S K T F H C E G G S I L A L L A G E N M E D . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D gea K M V Y R D V F P L V H R E L A Y W R R Q A E R I P D P E L R R Q A L A S I A S K T F H C E G G S I L A L L A G E N M E D . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D anl R R V Y R D V F P V V H R E L A Y W K R K A E A I P D P E L R R Q A L A S I E T K T F H C E G G S I L A L L A E E D I A P . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F Q TL H A anm R R V Y R D V F P V V H R E L A Y W K R K A E A I P D P E L R R Q A L A S I E T K T F H C E G G S I L A L L A E E D I A P . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F Q TL H A aamy K N V Y R D V F P I V H R E L E F W R K K A E K I P D A E L R K Q A L A S M N T K A F H C E G G A I L A L L A E A N R E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P L D F R AL H D afl R A V Y H R V F P L V H R E L A V W K K R A E A I P D E E L R K Q A L A S I A T K T F H C E G G G I L A L L A G K E M E R . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P T D F R AL H D agn R A V Y R R V F P I V H R E L A I W K K R A E A I P N E E L R K Q A L A S I A T K T F H C E G G A I L S L L A G K E M E R . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P T D F R AL H E bby A K V Y R D V F P V V H H E L A M W K E R A Y H I P N D E L H S Q A I A S I E H K T F H C E G G G I L A L L A N E H R E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P N D F A AL H E bce A K V Y R D V F P V V H H E L A M W K E R A Y H I P N D E L H S Q A I A S I E H K T F H C E G G G I L A L L A N E H R E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P N D F A AL H E ban A K V Y R D V F P V V H H E L A M W K E R A Y H I P N D E L H S Q A I A S I E H K T F H C E G G G I L A L L A N E H R E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P N D F A AL H E btk A K V Y R D V F P V V H H E L A M W K E R A Y H I P N D E L H S Q A I A S I E H K T F H C E G G G I L A L L A N E H R E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P N D F A AL H E bty A K V Y R D V F P V V H H E L A M W K E R A Y H I P N D E L H S Q A I A S I E H K T F H C E G G G I L A L L A N E H R E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P N D F A AL H E bwe A K V Y R D V F P V V H H E L A M W K E R A Y H I P N D E L H S Q A I A S I E N K T F H C E G G G I L A L L A N E H R E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P K D F A AL H E bmyc A K V Y R D V F P V V H H E L A M W K E R A Y H I P N D E L H S Q A I A S I E H K T F H C E G G G I L A L L A N E Q R E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P N D F A AL H E bcy A K V Y R D V F P V V H H E L A M W K E R A Y H I P N D E L H N Q A L A S I E H K T F H C E G G S I L A L L A N E Q R E E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P K D F A AL H E far Y S V Y T K V F P T V S Q L L Q D W R D Q A E K I P D P E L R Q Q A L S S I S N K M F H C E G G A I L T L L A G Q H R K K . A I E F V V A Y Q T I S D Y L D N L C D R S T . . . S L S E K D F R AL H E fpn Y S V Y T H I F P A V S H L L K D W H D R A E K I P N P E L R K Q A V S S I S D K M F H C E G G A I L T L L A G N H R K K . A I E F V V A Y Q T I S D Y L D N L C D R S T . . . S L N E K D F R AL H E sat T R I F L Q V R P R V K H Y L Q G W R Q R A E S I P D P E L R R Q A V M S I Q T K M F H C E G G A I Y A L L A G S H F D E . A A R F I I A Y Q T I S D Y L D N L C D R S T . . . S L N P S D F R AL H Q len S E T Y F K V L P A V R K N L H H W N T Q A E Q I P N P E L R K Q A L A S L S D K Q F H C E G G A I Y G L L A K S H W R E . A I R F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P E D F R AL H E glj S Q M H D K V L P L V R R C L N R W L L Q A R Q I P N P E L R K Q A L A S L E A K Q F H C E G G A I Y G L L A N R D W Q E . A V R F I V A Y Q T I S D Y L D N L C D R S N . . . S L D P E D F R AL H G npu L R I Y C D V L P R V R K H L E F W K K N A E Q I P N P E L R K Q A L L S I R T K T F H C E G G S I Y G L L A K E E I E P . I I C F I V A Y Q T I S D Y L D N L C D R S N . . . S L D P K D F R TL H Q bco F H V Y K F V L P K V H E Y L Q F W K K K A Q E I P N E E L R K Q A L A S I E S K T F H C E G G S I Y G I L A K E R R D E . V I E F V V A Y Q T I S D Y L D N L C D R S T . . . S L D P N D F R AL H E bse M R V Y R D V I P Q V H R E L A V W K Q K A A S I P D E E L R T Q A L A S I R E K T F H C E G G G I L S L L A G P N Q R R . L I R F I T A Y Q T I S D Y L D N L C D R S D . . . S M D P E D F R SL H Q axl K T A V K K I I P A V N E E L H Y W H T R A E K I P N P N L R K Q A L Q S I E A K A F H A R G G G I Y A M L A K D K W R E . A I T F I V A Y Q T I S D Y L D N L C D R S D . . . S L D P I D F R SL H Q tap H Q V Y R K I F P E V H K E L E L W T Q R A E A I P D P E L R K Q A L E S I R T K R F H C Q G G A V Y S L L A G D A W K Q . A I K F I I A Y Q T I S D Y L D N L C D R S T . . . S L D P E D F R LL H Q hhd F R V Y K E V F P E V H K E L N Y W V E R A K K I P N K E L R T Q A I A S I E D K T F H C E G G S I Y S M L A G P Q W K E . S I R F I V A Y Q T I S D Y L D N L C D R S T . . . S M D P I D F R ML H Q vig I T V Y R K I F P A V S K E L A V W K Q R A D E I P D E E L R F Q A L A S M S E K R F H C Q G G A V Y A L L S G A R W R E . C I R F I V A Y Q T I S D Y L D N L C D R S T . . . T L D P S S F S LL H T lao T A V Y R K I F P A V N A E L N F W Q K R A G A I P N E E L R Q Q A L A S I E S K R F H C L G G A V Y A L L S G F R W R E . A I T F I V A Y Q T I S D Y L D N L C D R S T . . . S L D P D D F Q QL H E sje Y Q G Y R F I F P E V Y R Q L E A W K E R A A D I P D P E L R F Q A T D S I E K K A F H C E G G G L F S L L S G A Q W K E . T V T F V V A Y Q T I C D Y L D N L C D Q S E . . . S L D P K D F E SL H F tur T A F Y K S Y Q P K T K S F L S L Y E Q H A Q Q I T D P K L K K E A L A S L S K K A F H C Y G A S F Y A A L V S E E Y Q A D Y L K F M T A Y Q T M C D Y L D N L V D Q T N . . . V I N E T N F R RL H Q say R E Y L T A V R P T V A R Y L A E W Q T Q A T A I E H S A L R T Q A L S S L T T K Q F H C E G G G I F S S P S R . D P E Q R L L P F I V A Y Q T A C D Y L D T I T D R G . . . P S Q A P D N L R QL H Q tmr A T Y V G R V L P A V D R A L D R W Q A R A A L I P D P E L R R Q A L A S L R T K R F H C E G G A V F A A A V P P D R R A T L V E A I V A L Q T I S D Y L D N L C D R S . . . E S L D P A D Y R QL H Q lpil T R L F G R V L P Q A R R E L E R W T R A A R A I P D P H L R A Q A L A S L R F K R F H A L G A S V F G A Q A R . . E M G A F V R F A V A Y Q T I S D Y L D N L S D R D R V P G T R L E E D L T LL H Q aac Y R L F R R V M P L V R A E L A G W R A R A E A I P D G L L R E Q A L A S L R D K Q F H A D G G S V Y A A A N P . D H M H H L V Q A I V S L Q T I S D Y L D N L C D R A G . . . V S D P V A F R VL H Q nth S L M I F K V L P F V N R E L N Y W Y D V I S N A S S D F L S E Q G Q L S I K F K K F H C Q G G S V Y S L Y K G S F D E D . V A R F I V A F Q T I S D Y L D N L C D R S G . . . I Y E E R S F A KL H Q ctx L K C I S D I Y P K S R S L F R E Y G . . . . . I F E D K Y D N M E G F S L Q M K K L P A R E A G I Y A L Y P G V N L D N . T L D F I I S F Q T I D R C I N H I C S K I K . . . D K D E L L I G RL Y L clb N R Y V K R I N P I V E K K S E E Y Y N Y T G R I V K Y N I K K N A V E A L K Q S S L D M A V S S V C T F W P G V N V N L . A S E V I F S F M A V V R Y L N K I C E N S S . . . V V T E A F I R VV F S Fig. S4. (2/6)

S11 1 1 0 1 2 0 1 3 0 1 4 0 1 50 BalTS A L L A A L T P . G E P ...... L V N Y Y Q Y R I E Q E D G G Y L H E L I E T C Q H I L V T FP S F dor A M Q E A L R P G V A P S ...... N Y Y L F Y P Y R E D G G Y L E L L V K T C Q D S V R K LP S F dmi A M Q E A L N P E A D L S ...... D Y Y L Y Y P Y R E D G G Y L K N L V Q T C Q E S L R N LP S Y dai A M E E A L V F K A N L S ...... D Y Y K Y Y P Y Q N D G G Y L E Q L V K T C Q A S L K S LP S F ddh A M T E A L D A G T Q C S ...... D Y Y A Y Y P Y H E D G G Y L V E L V Q T C Q R R V Q K LP S Y dsy A M T E A L D A D A R C S ...... D Y Y A Y Y P H R E D G G Y L A E L V Q T C Q R R V Q K LP S Y ddl A M T E A L D A N A K C S ...... D Y Y A Y Y P Y H E D G G Y L K A L V Q T C Q R R V Q D LP S Y puf A M T D A L T P D A L P Q ...... D Y Y A Y Y P F K E D G G Y L K Q L V I T C Q Q Q I R A LP S Y pft A M T D A L D P S A H L K ...... D Y Y A F Y P Y K E D G G Y L K E L V L T C Q E K V N T LP S Y gfe A I T D A L H R E E D Y K ...... D Y Y A F Y P Y E E D G G Y L Q R L V S T C K E Y I R T LP S Y toc A M I D A L L P G E S Y N ...... D Y Y K Y Y P Y R N D G G Y L T L L V S E C K K F I S T LP S Y mas A M T D A L L P D E Q Y S ...... D Y Y S Y Y P Y S Q D G G Y L R Y L V K E C K N V I N L IP A Y tpz A F T D A L E P E G G ...... T S G Y Y D L F P F K D D G G Y L D A L V A E C R R V L R R LP S Y dau A F L C A V D D E R E ...... V P D F Y Q L Y P F G G D G G Y L R S L V E V C R G V T A D LP A Y mta A V T D A L I P G G A ...... G H D Y Y A A Y P Y H R D G G Y L R A L V R A C R E S L A A LP G Y dku A F V D A L C P G A S ...... G C D Y Y A L Y P Y Q E D G G Y L Q E L V R S C Q Q A L A R LP A Y slp A I V V A L A P E A P ...... L V D F Y E H Y A D A E E K C Y L P A L V R A C Q K I A A S LP R L swo S L E D A L S P V E A S L ...... L P D Y Y S Y Y P S Q E D G G Y I E K L V R V C Q S C V K Q LP S Y blr S M Q D A L T P . D A P ...... L R D Y Y E F R E E K D D G G F L N A L V L R C Q E M V R N LP S Y bbe S M Q D A L T P . G A P ...... L R D Y Y L Y R E D K D D G G F L A G L V Q T C Q Q H V A Q LP A Y pnp S M L D A V D P . S A P ...... L H D Y Y E F H K E Q E D G N Y L N E L V K T C Q A S I R M LP S Y pms S M L D A V D P . S E P ...... L H E Y Y A F R G E R E D G G Y L N D L V K T C Q A S I R L LP S Y plv S M L D A V D P . D E P ...... F H D Y Y A C R M E K E D G G Y L R S L V E T C Q K E I R G LS S Y pow A M L D A V D P . T S P ...... L T D Y Y A Y R N E R D D G G Y L H M L V E T C R Q C V S R LP S F pbj S M L D A V N P . G T A ...... L Q D Y Y A L R K E R D D C G Y L H H L V Q M C Q Q S V A R LP S Y pjd S M L D A V D P . S A V ...... V K D Y Y A L R Q E R N D G G Y L H H L V N L C Q H C V S M LP S Y pdu S M L D A I T P . G A E ...... P V N Y Y A L R S E Q N D G G Y L H R L V R T C Q E M I S R LP G Y psab S M L D A I T P . G A E ...... P V N Y Y A L R S E Q D D G G Y L Y R L V R T C Q E M I S K LP G Y pste S M L D A V T P . G A E ...... P V N Y Y A L R A E Q D D G G Y L H R L V R N C Q D M I D K LP G Y paee S M L D A I T P . G A E ...... P V N Y Y A L R S E Q N D G G Y L H R L V R K C Q E M T A L LP G Y paea S M L D A I T P . G A E ...... P V N Y Y A L R S E Q N D G G Y L H R L V R K C Q E M T A L LP G Y paeq S M L D A I N P . E A E ...... P G N Y Y E L R N E Q N D G G Y L Y R L V R K C Q E M T S Q LP G Y paen S M L D A I N P . E A E ...... P V N Y Y A L R N E Q N D G G Y L Y R L V R K C Q E M T S Q LP G Y pbd S M L D A I N P . G A E ...... P V N Y Y A L R N E Q N D G G Y L Y R L V R K C Q E M T S Q LP G Y paeh S M L D A I T P . G A E ...... P V N Y Y A L R S E Q N D G G Y L Y R L V R K C Q E M T A L LP G Y pgm S M L D A I N P . K A E ...... L V N Y Y A L R S E Q N D G G Y L H R L V R K C Q E M T A L LP G Y pri S M L D A I N P . K A E ...... P V N Y Y A L R S E Q N D G G Y L H R L V R K C Q E M T A L LP G Y paej S M L D A I D P . N A E ...... P V N Y Y A L R D E Q N D G G Y L Y R L V R K C Q E M I S L LP G Y paef S M L D A I D P . N A E ...... P V N Y Y A L R D E Q N D G G Y L Y R L V R K C Q E M I S L LP G Y pod S M L D A I D P . N A E ...... P G N Y Y A L R S E Q N D G G Y L Y R L V R K C Q E M I S L LP G Y gym S M L D A V T P . E M E ...... P A D Y Y A L R S E R E D G G Y L L R L V Q K C R D C I G Q LS G Y ppeo A M L D A V N P . T A R ...... P V N Y Y E L R R E Q E D G G Y L T G L V T T C Q S C V S R LP G Y ppy A M L D A V N P . T A R ...... P V N Y Y E L R R E Q E D G G Y L T G L V T T C Q S C V S R LP G Y pta S M L D A V D P . A A K ...... P V N Y Y A L R R E Q E D G G Y L T G L V T T C Q S C V S R LP G Y pih S M L D A I N P . D A L ...... P L H Y Y A F R Q E Q N D G G Y L L K L V E T C H S C I R L LP G Y pbv S M L D A V T P . D A Q ...... P V N Y Y R L R T E Q E D G G Y L E A L V T T C Q Q N V S K LP D Y tco A M L D A V D P . D A E ...... T T D Y Y A H R A E R D D G G Y L A A L V A A C Q E N I R R LP G Y anx A M L D A V S G . R F S ...... S V D Y Y E F N R E K D D G G Y L R A L V A A C H A E I E H LP N Y bpf A L L T A L T P . G A P ...... L E N N Y E F R N E Q E D G G Y L H A L I E T C Q Q I L S T FP S F bha A L L A A I N D . E A P ...... L E N Y Y R F R E T Q D D G G Y L H D M I H I C R S A L Q K LP S F bcl A L L D C L T P . D K P ...... H G D Y Y Q Y R D H F E D N G Y L R K L V D A C R E A T A S FP G F ble A L L D T L E P . E K E ...... F S D Y Y Q Y R P G F H D D G Y L Q K L V T R C R E A V Q Q FP G F bmet S M T D A L S L . N A V ...... P K N Y Y R F R K E Q D D G N Y L A D L A E T C R S V L M K VN H Y gst S M S D A L K L . Q E V ...... N K N Y Y R L R E D Q D D D G Y L H D L S K T C R T I L R E IE H Y baci A M K D A L C L . S V A ...... P K N Y Y R Y R E D Q D D G G Y L A E L S G A C R A V L Q E MH H Y bif A M E D A L S L . E P G ...... S G D Y Y R E R Q E K E D G G Y L A E L A G A C R G M L R G CR H Y bsm S M I D A L T V . G A P ...... F R P Y Y R F R N E Q E D G G Y L R E L V G T C Q S V L Q K IN H Y bck S M S D A L T V . G A P ...... L K N Y Y R H R Q D Q D D G G Y L H E L V R T C Q V V L S R IP Q Y jeo A M E D A L T V . G K V ...... P R D Y Y R M R S D R E S . H Y L S G L V L R C Q E V L S R IP N Y bmq S M P D A L T P . H A P ...... L G D Y Y R F R A D K D D G G Y L A G L V Q T C Q Q S L R K AC N Y beo S M P H A L T P . H A T ...... L G E Y Y R Y R E D Q N D G G Y L H A L V Q T C Q E V L A S IE H Y bacy S M Q D A L T V . G A E ...... L Q N Y Y Q F R E E Q D D S G Y L H E L V K T C Q R V L G S IE H Y bsus S M Q D A L T V . G A E ...... L Q N Y Y Q F R E E Q D D S G Y L H E L V K T C Q R V L G S IE H Y balm S M Q D A L T V . G A E ...... L Q N Y Y Q F R E E Q D D S G Y L H E L V K T C Q R V L G S IE H Y bjs S M Q D A L T V . G A E ...... L Q N Y Y Q F R E E Q D D S G Y L H E L V K T C Q R V L G S IE H Y bacl S M Q D A L T V . G A E ...... L Q N Y Y Q F R E E Q D D S G Y L H E L V K T C Q R V L G S IE H Y bae S M L D A L T V . G A E ...... L Q N Y Y Q F R N E Q D D S G Y L H D L V K T C Q R V L G S IE H Y bacp S M R D A L T V . G A E ...... V R P Y Y Q Y R D E R D D G G Y L H E L V R T C Q R V L G S IE H Y bacb S M R D A L T V . G A E ...... V R P Y Y Q Y R E E R D D G G Y L H E L V R T C Q R V L G S IE H Y bay S M R D A L T V . G A E ...... V R P Y Y Q Y R D E Q D D G G Y L H E L V R T C Q R V L G S IE H Y bao S M R D A L T V . G A E ...... V Q P Y Y Q Y R E E Q D D G G Y L H E L V R T C Q R V L G S IE H Y bli S M K D A L T V . G A E ...... L K N Y Y R F R E D Q D D Q G Y L H D L V K T C Q G V L A E IE N Y blh S M K D A L T V . G A E ...... L K N Y Y R F R E D Q D D Q G Y L H D L V K T C Q D V L A E IE N Y bgy S M K D A L T V . G A E ...... L K N Y Y R F R E D Q E D C G Y L H E L V K T C Q D V L A D IE N Y bacw A M R D A L D I . H A E ...... L K P Y Y Q F R E D Q E D H G Y L H A L V R T C Q D V L T R VE H Y bpu A M R D A L D I . H A E ...... L K P Y Y Q F R D D Q E D H G Y L H A L V R T C Q D V L S R LK H Y gth S M P D A L T V . D A G ...... V S N Y Y R H R Q E Q D D G G Y L H D L V R T C Q S V L K K VT H Y gmc S M P D A L T V . D A G ...... V S N Y Y R H R Q E Q D D G G Y L H D L V R T C Q S V L K K VT H Y gwc S M P A A L S I . D A D ...... V S N Y Y R H R Q E Q D D G G Y L H D L V R T C Q D V L K K VM H Y gtn S M P D A L T I . G A E ...... P S N Y Y R Y R R E Q E D G G Y L P D L V R T C Q E V L A T VR H Y gsr S M P D A L T L . G A E ...... P S N Y Y R H R R E Q E D G G Y L P A L V R T C Q E V L K T VR H Y gjf S M P D A L T I . G A E ...... P S N Y Y R H R R E Q E D G G Y L P D L V R T C Q E V L G T LR H Y gse S M P D A L T I . G A E ...... P S N Y Y R H R R E Q E D G G Y L P A L V R T C Q K V L E T VR H Y gct S M P D A L T I . G A E ...... P S N Y Y R H R R E Q E D G G Y L P A L V R T C Q K V L E T VR H Y gya S M P D A L T I . G A E ...... P S N Y Y R H R R E Q E D G G Y L P A L V R T C Q K V L E T VR H Y gyc S M P D A L T I . G A E ...... P S N Y Y R H R R E Q E D G G Y L P A L V R T C Q K V L E T VR H Y gte S M P D A L T I . G A E ...... P S N Y Y R H R R E Q E D G G Y L P A L V R T C Q E V L E T VR H Y gka S M P D A L T I . G A E ...... P S N Y Y R H R R E Q E D G G Y L P A L V R T C Q E V L E T VR H Y ggh S M P D A L T I . G A E ...... P S N Y Y R H R R E Q E D G G Y L P A L V R T C Q E V L E T VR H Y gej S M P D A L T I . G A E ...... P S N Y Y R H R R E Q E D G G Y L P A L V R T C Q E V L E T VR H Y gel S M P D A L T I . G A E ...... P S N Y Y R H R R E Q E D G G Y L P A L V R T C Q E V L E T VR H Y gea S M P D A L T I . G A E ...... P S N Y Y R H R R E Q E D G G Y L P A L V R T C Q E V L E T VR H Y anl S M P D A L R T . D A I ...... P F N Y Y R H R N E Q N D G G Y L W E L V H T C Q N V L K Q VK H Y anm S M P D A L R T . D A I ...... P F N Y Y R H R N E Q N D G G Y L W E L V H T C Q N V L K Q VK H Y aamy S M P D A L C I . D A V ...... P T N Y Y R Y R S E Q N D G G Y L H E L V Y T C Q D V L K K VP H Y afl S M I H A L T V . G A K ...... K E T Y Y R Y R A E Q D D G G Y L H A L V D T C Q E M L E G VQ H Y agn S M M H A L T V . G A K ...... K E A Y Y R Y R T E Q D D G G Y L H A L V D T C Q E T L A E VR H Y bby S M L M A L S P . E V E G ...... G G N Y Y R Y R D D Q D D G G Y L D E L V E T C Q D V L K K TK H Y bce S M L M A L S P . E V E G ...... G G N Y Y R Y R D D Q D D G G Y L D E L V E T C Q D V L K K TK H Y ban S M L M A L S P . E V E G ...... G G N Y Y R Y R D D Q D D G G Y L D E L V E T C Q D V L K K TK H Y btk S M L M A L S P . E V E G ...... G G N Y Y R Y R D D Q D D G G Y L D E L V E T C Q D V L K K TK H Y bty S M L M A L S P . E V E G ...... G G N Y Y R Y R D D Q D D G G Y L D E L V E T C Q D V L K K TK H Y bwe S M V M A L S P . E V E G ...... G G N Y Y R Y R D D Q D D G G Y L D E L V E T C Q D V L K K TK H Y bmyc S M L T A L T P . E S E ...... G S N Y Y R Y R D D Q D D G G Y L D E L V A T C Q D V L K K TK H Y bcy S M L M A L T P . E S E S ...... G G N Y Y R Y R D D Q D D G G Y L D E L V A T C Q D V L R K TK H Y far S M F H A L S P . G V K ...... P V N Y Y R Y R D E Q E D G G Y L A D L V L A C Q K V L S E MQ A Y fpn S M F H A L S P . G A V ...... P T N Y Y R F R E E Q D D G G Y L N E L V Y T C Q N V L A E MK A Y sat S M L H A L T P . S A R ...... L G N Y Y H L R Q E Q N D G G Y L A G L V R T C Q D V L A K LP A Y len A A I D A L T P . D A E ...... G K N Y Y R C R A D Q D D G G Y L Q C L V R T C Q E V L R Q LP N H glj S I L H A L T P . S A E ...... L S N Y Y R F R R D Q D D G N Y L I S L V K D C Q I I L S N TL N Y npu A C L D A L T P . S A K ...... C I N Y Y Q F R Q E Q D D G G Y L M K L V K T C Q N V L R Q LP S Y bco S M P D A L T P . G A E ...... V K D Y Y R F R E E K D D G G Y L E S L V K T C Q K C I S K FP S Y bse A M L D V F D P . A G Y ...... M G D Y Y A F R T H E G D R G Y L R D L V I V C R E E L V A LS N Y axl S M L S I F N L . S N E ...... T I N Y Y H H R Q D Q D D G G Y L D E L V R V C Q K Q L R Q LP D Y tap S M L D A L Q P . G E K ...... L K D Y Y A L R D E R E D G G Y L H S L V F T C Q T I L S K QS N L hhd S M A D A L T P . E N E ...... I K D Y Y H Y R D D K D D G N Y L S D L V H T C Q N V L K D SS D Y vig S M I D A H C P . R S E ...... P K D Y Y A F F H H K Q D N G Y L Q Q L V Q T C N D V V A K LD D I lao A M S D A L S R . Q N P ...... I Q N Y Y A L R D E Q S D G E Y L A D L V R T C Q R T M R R LD A Y sje A L E D A V H P . D Y E ...... H R D Y Y A F R E E K E D G G Y L S E L V S T C Q G V L S R FP F Y tur S L L D V F K L . T P H ...... A P N Y Y Q Y Q T Q Q L D G G Y L N M L V R L C Q E S L K K IP H Y say A L L D A V T P G K S P E ...... A Y F R S H P D G D D G G Y L T R L V T R C Q T E V A T WP G W tmr A M L D A V T P W P A Q A P A S V P R R A V M P P P H R G Q A P L P S R A E A P L P R L A T V P A P H R G A P P S A D E G T A G S G G R A Y Y R L H P H Q D D G G Y L A A L V T S C R T A L A A FP G Y lpil A M I D A V S P S N P A S ...... G Y Y R L H T A T D D G G Y L P D L V A T C R E A L G A LG . A aac S L Q D A V H P G T T P A ...... D Y Y R H Y A H R E D G G Y L A S L V R T C Q Q A L E Q LP H Y nth A M L D I F N T D E V N L S V S ...... G E G Y Y K Y Y P H T D D D S Y L I N L V Q T C R Q E L S K FK E I ctx S L R D A V D P K R R I S ...... V G Y I N G L D S K Y V S T I I K L V E R C R N Q V V M LP S Y clb S L K D A A N I R N E S ...... F E K Y F T F F P S K D D N G Y L S I L V E K C R Q K I Q L LP S Y

Fig. S4. (3/6)

S12 8 0 2

1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1G 0 2 2 0 2 3 0 2 4 0 BalTS R M V Q E N M L E L S Q L Y G D L Q V H K H V V K E . E R I P R L E A W F N E H K . . . E K M P E M T W F E F S A C T G S T L G V Y T L A T Y A T K E G . L T S E Q A D V I K A G Y F P W V Q G VH L L dor A I V Q E D A V K L A E L Y S Y L Q T Y K H L A V N . V R E S K M L G W I N P H I A . . . D N Q E I T V W E F A A A A G S T L G I F C L Y A A A F N P E . L T L E Q V K R I N E T Y F P W I S G LH I L dmi Q T V Q G E A I K L A E L Y S S L Q T Y K H L A V S . E R E G K M V D W I T P H L A . . . A D S E I T I W E F A A A S G S T L G I F C L F S V A H D P K . L S L K Q V E T I S Q T Y F P W I C G LH I L dai H L V Q E N A L E L A R L Y S H L Q T Y K H L E A E . R R E S V M L D W I D P Y L R . . . K Y P S I T S W E F A A A T G S T L G I F C L Y A A S F D I D . L Q A S D V D K I C Q A Y F P W I C G LH I L ddh G V I R P F M M E L A E L Y S M L Q V T K H L H P A . E R E K K M L S W L D K V I T . . . K Y P G L S A W E L A A A T G S T L G T F C L F G M A Y D P R . L T E N E A K K T K E A Y F P W I T G LH I L dsy E V V R P Y M M K L A E L Y T L L Q V S K H L H P A . E R E Q K M L G W L E Q V I P . . . E Y P G L S V W E L A A A T G S T L G T F C L F A M A Y D A Q . L T D R E A K K V R D A Y F P W I T G LH I L ddl P T I K G S M L E L A E L Y A M L Q T T K H L Q P S . V R E E K M L R W L N Q L L S . . . N Y P G L S P W E L A A A T G S T L G I F Y L F A L A Y S P D . L T E S D V K Q A K N A Y F P W I A G LH I L puf E L V K S E I Q K L A C L Y S E L Q T Y K H L D P S . I R E V K M T N W I T H H I G . . . D Y P Q I T P W E F A A A T G S T L G M F M L C A A A S D K N . L H P H T V K V I D S A Y F P W I S G LH I L pft E L V K P N I Q K L A R L Y S E L Q T Y K H L N P S . I R E E K M L T W I H K H L E . . . H S P Q L T P W E F A A A T G S T L G M F M L C A A A S D K N . L T S C T V S K I D S A Y F P W I S G LH I L gfe P L V Q E E V L Y L G G L Y S E M Q A Y K H T S L S . V R E K H M Q L W S K P H L I . . . K Y P E L S T W E F S A A A G S T L G I F M L C T L A R N P D . L T K N K V T Q V M D A Y F P W V C G LH I L toc T V I R E K I L F L A R L Y S D L Q V Y K H L A P E . I R E C R M A G W F S N Y L D . . . Y F P E I S G W E F S A A A G S T L G I F M L V A A A A D P E . L D N L E A W K I F Q S Y F P W I C G LH I L mas D V I K D K I L Y L V G I Y S D L Q V Y K H L T H D . I R E D K L I K W S A V H I D S . . S Y P K L N W W E F A A A S G S T L G I F V L V A C A F D T N . L R A E T V Q G I Y D A Y F P W I C G LH I L tpz P V V K D A A L R L A S L Y C D L Q T Y K H T H A A . L R E K Y L E E W F A A H R D . . G C G D . L D W W E F A A A T G S T L G I F A L V A A A G R E G . L D P A A A G E I A A G Y F P W I C G LH I L dau R L V R D D V L R L A E L Y C D L Q V Y K H T E L W . A R E P L L I S W F N R H R G . . R Y P G . I E W W E F A A A A G S T L G I F G L L A S A T R P E . L E R R E V N A L V K A Y F P Y V C G LH I L mta E L V R E E A L Y L A D L Y C R L Q A T K H T Y P D . R R R E R L Q V W L R P L L G . . Q I P A P L Y W W E L A A A T G S T L G I F A L M A L A A R G E . T Q A R D V A G V K A A Y F P W I G G LH I L dku G P L R E R A C R L A E L Y C Q L Q V Y K H I Q W P . L R V K S L T T W L E P L L E . . S L P E R L Y W W E L A A A T G S T I G I F A L F A L A A R G N . Y T A D E V E R V T A A Y F P W I C G LH I L slp E L V R D R L I E L V R Y Y S N L Q V L K H L P V G . Q R Q E R L E A Y I K K E V P . . D Q Y G . L A W W E L A A A T G S T L G V F G L M A L A A H P D . C A P A W A E G L Y H A Y F P W I C G LH I L swo P A V Y P D L I H L V R L Y I D L Q V I K H I D P W . Q R E E E L R E W A K K Q L Y . . A Y P G . L R W Q E F A A A A G S T L A V F A L F G L A S I Q D . L P P V E S R K V V E N Y F P W I C G LH I L blr K D V Q Q H I V N L S T L Y S D L Q V Y K H I A L E . K R E E A L L T W W D Q Y K . . . E S Y P E I E W Q E F A A A T G S T I G I F A L F C L A T E P A . V D P K E I E A L H H A Y F P W I G G VH I L bbe E K I Q A K I L E F S C L Y S D L Q V Y K H I A P H . L R E D H L L T W W D Q Y K . . . D R Y H D L H W Q E F A A V T G S T I G I F A L F C L A T D P D . V G E E Q I Q T V S E A Y F P W L C G LH I L pnp A P A A S S V R E L V S L Y C D L Q V Y K H M A K P . L R E D A L L S W W E M H R . . . E R Y P S I G W N E F A A A T G S T L G V F V L F L A A S E P E . L S P E T V R N I H V A Y F P Y I C G LH I L pms A L V A G Q V R E L V G L Y C D L Q V Y K H I R P D . L R E E S L L R W W E G H R . . . N R Y P S I A W N E F A A A T G S T L G M F M L F L A A S E S E . L A P Q T V E E I R E T Y F P Y I C G LH I L plv P V V K D K V R E L V S L Y C D L Q V Y K H I Q A D . L R E N E L H R W W K G H L . . . A S Y P D I S W N E F A A A T G S T L G V F M L F Q A A S N P D . L D K E Q A R Q I V E A Y F P Y V C G LH I L pow A V V Q P Y V T E L V G L Y G D L Q V Y K H I R F D . L R E S R L L E W W A L H R . . . D R C P Q L S W N E F A A A A G S T L G M F A L F L A A S R P G . L T D E A A R T F R D A Y F P H V C G LH I L pbj N K V R P Y V T E L V G L Y G D L Q V Y K H I R K D . L R E P K L M Q W W E L H R . . . S R Y A H L Q W N E F A A A T G S T L G M F M L F L A A A D A G . L T D E Q A V Q I R D C Y F P H L C G LH I L pjd A A A Q P Y V T E L V G L Y T D L Q V Y K H I R K D . L R E E S L L T W W E P Y A . . . D R Y P G L Y W N E F A A A T G S T L G M F M L F T A A S D K T . L R P E D A E A I K N I Y F P H V C G LH I M pdu M T A A S E I Y D L A A L Y T D L Q V Y K H I R P E . M R E A A L K E W W E E N R . . . S R A P Q L Y W N E F A A A T G S T L G V F M L F L A S C D S S . L T K P D V S L I R S G Y F P H L C C LH I M psab A S A A S E I S G L A S L Y T D L Q V Y K H I R H D . L R E A A L K E W W E E N R . . . S R A P R L H W N E F A A A T G S T L G I F M L F L A S C D S R . L S K P D A S L I R A G Y F P H L C C LH I M pste A S A A Q E I Y D L A E L Y T D L Q V Y K H I R P D . L R E S A L Q K W W E E K R . . . G R A P H L Y W N E F A A A T G S T L G V F M L F L A S C D P R . L K K E D A S Q I R A G Y F P H L C C LH I M paee A A A A E E I Y D L A V L Y T D L Q V Y K H I R P E . L R E A A L K E W W A A E G . . . K R A P H L E W N E F A A A T G S T L G V F M L F L S A C D P R . L D K S K A A S I R A A Y F P H V C G LH I M paea A A A A G E I Y D L A V L Y T D L Q V Y K H I R P E . L R E A A L K E W W A V E G . . . K R A P H L H W N E F A A A T G S T L G V F M L F L S A C D P R . L D K S K A A S I R A A Y F P H V C G LH I M paeq A A A A A E I R D L A V L Y T D L Q V Y K H I R P E . L R E A A L K E W W E R E G . . . H R A P H L G W N E F A A A T G S T L G V F M L F L A S C D P K . L S L D A S A S I R A A Y F P H V C G LH I M paen A A A A A E I H D L A V L Y T D L Q V Y K H I R P E . L R E A A L K E W W E R E G . . . H R A P H L G W N E F A A A T G S T L G V F M L F L A S C D P K . L S L S A S A S I R A A Y F P H V C G LH I M pbd G A A A A E I H D L A V L Y T D L Q V Y K H I R P E . L R E A A L K E W W E K E G . . . H R A P H L Q W N E F A A A T G S T L G V F M L F L A S C D P K . L S T S S S A S I R A A Y F P H V C G LH I M paeh A S A V A E I H D L A V L Y T D L Q V Y K H I S P E . L R E D A L K E W W A K E G . . . K R A P H L Q W N E F A A A T G S T L G V F M L F L A S C D P K . L T K S A S V S I R A A Y F P H L C G LH I M pgm A A A V E E V R G L A V L Y T D L Q V Y K H I R P E . L R E A A L K E W W E V E G . . . Q A A P H L Q W N E F A A A T G S T L G V F M L F L A S C D P K . L S T S A A A S I R A A Y F P H L C G LH I M pri A A A V E E V R G L A V L Y T D L Q V Y K H I R P E . L R E A A L K E W W E V E G . . . K V A P H L Q W N E F A A A T G S T L G V F M L F L A S C D P K . L S T S A A A S I R A A Y F P H L C G LH I M paej S A A A A E I R D L A V L Y T D L Q V Y K H I R P E . L R E T A L K E W W E Q Q G . . . S R A P H L H W N E F A A A T G S T L G V F M L F L S A C D P K . L S K S S S E S I R A A Y F P H V C G LH I M paef S A A A A E I R D L A V L Y T D L Q V Y K H I R P E . L R E T A L K E W W E Q Q G . . . S R A P H L Q W N E F A A A T G S T L G V F M L F L S A C D P K . L S K S S S E S I R A A Y F P H V C G LH I M pod S A A A A E I R E L A V L Y T D L Q V Y K H I R P E . L R E T A L K E W W E E Q G . . . S R A P H L Q W N E F S A A T G S T L G V F M L F L S A C D P K . L N Q A S A A S I R A A Y F P H V C G LH I M gym E A A K P Y I R D L A G L Y T D L Q V Y K H I H P D . K R E A A L L E W W S R H A . . . H R T P H L R W N E F A A A T G S T L G V F M L F L A A T D P F . L D D E D A S S I H A S Y F P N V C S LH I M ppeo E A A M P Y V Q D L A R L Y T D L Q V Y K H I K P E . L R E Q A L L D W W S L H K . . . D R T P E L R W N E F A A A T G S T L G V F M L F L A A S D Q H . L T D A G A A S I H A S Y F P H V C S LH I L ppy E A A M P Y V Q D L A R L Y T D L Q V Y K H I K P E . L R E Q A L L D W W S L H K . . . D R T P E L R W N E F A A A T G S T L G V F M L F L A A S D Q H . L T D A G A A S I H A S Y F P H V C S LH I L pta E A A M P Y V Q D L A G L Y T D L Q V Y K H I K P E . L R E Q A L L D W W S V H K . . . G R T P E L R W N E F A A A T G S T L G V F M L F L A A S D R H . L T D A G A A S I H A S Y F P H V C S LH I L pih A I A L P F I Q D L V G L Y T D L Q V Y K H I D P E . L R E E A L L N W W S I H R . . . D R T P Q L G W N E F A A A T G S T V G V F M L F L S A T D P H . L D Q A T V A T I H S S Y F P H V C C LH I M pbv D A V F P Y V R D L V G L Y C D L Q V H K H I A P E . L R E S A L L N W W S E N K . . . Y R T P H L Q W N E F A A A T G S T L G V F M L F L A A S G F G . L D D T G A K Q V Y S A Y F P H V C C LH I M tco A K V Q P H V A R F A G L Y G D L Q V Y K H I R R E . E R L E S L H R W W A L H R . . . T D H P E L Y W N E F A A A T G S T L G M F A L F V E A C R P D . V T E R D A E R M A G A Y F P Y L C G LH I L anx A L V R D D V Y E L A S L Y C N L Q V H K H V V Q E . E R E G R L L N W W Q E H R . . . G K A P D L K W N E F A A A A G S T L G V F H L F Q I A S Y P E . V S A S R I A F I K K A Y F P W V C S LH I L bpf K K M Q P A M L E L S G Y Y C D L Q V Y K H V K K E . D R I P M L K A W Y E R H R . . . H K M P E M T W Y E F S A C T A S T L G V Y A L A T Y S T K P N . M T S E T A E T I K A G Y F P W V Q G FH I L bha S I V Q P Y M L K L C Q Y Y C D F Q T Y K H V K K E . D R V P M L E A W F E R H R . . . D E V P A M S W Y E F A C C T G S T L G I Y T L T V Y G G K Q G . F T D R Q A R Q L M D G Y F P Y V Q G VH L L bcl A D M Q T H M Q E V S Q F Y I D F Q V Y K H V E E E . K R E P L L K D F Y E R N K . . . H F A P T M R W Y E F A C G T A S T L A L Y C M A A Y A A A P V . Q T A Q . G Q Q I K E A Y F P W V Q G VH I L ble N V M K D D M K E V A R Y Y I D F Q V Y K H V E E E . K R E P L L K A F Y E E N Q . . . H L V P G M R W Y E F A C G A A S T L A L Y T L A A Y A A A S E . R T K E E S K H I K E A Y F P W V Q G LH I M bmet H I I S H H L L E L C R Y Y C D L Q I H K H V V E E . E R I T R L R N W F D N N K . . . E K I P Q M E W Y E F S A C S G S T L G I F C L V S Y A M R D D . F R L E D A E N I K N G Y F P Y I Q G LH I L gst D L I K D Y L L E L C E Y Y C D L Q I H K H V K E E . E R V G R L E K W F Q Q Y Q . . . K Q L P D M E W Y E F S A C S G S T L G I F C L V S Y A M R K D . F T A S D A A N I R K G Y F P Y I Q G LH I L baci P K I S S F L T E L C E Y Y C D L Q I H K H V V V E . E R V P R L K Q W Y L L N Q . . . D N I P E M E W Y E F S A C S G S T L G I F C L L S Y A M R D D . F E D D H A E K I K N G Y F P Y I Q G LH I L bif E S I R S Y L K E L C R Y Y S D L Q I H K H V C P E . E R V N R L Q N W H A E Y R . . . G L V P E M E W Y E F S A C S G S T L G I F S L V S C A L S D E . F A E E D A A K I R R G Y F P Y I Q G LH I L bsm P A I S S Y L L E L C R Y Y C D L Q I H K H V C V E . E R E E R L K K W F S R Y K . . . D Q L P K M E W F E F S A C S G S T L G I F C L V S Y A F R D D . F K P E Y A S M I R E A Y F P Y I Q G LH I L bck K A I Q P Y L L E L C R Y Y S D L Q V H K H V R V E . E R V P R L K E W F L H Y K . . . A D F P D M E W Y E F S A C S G S T L G I F C L V S Y A L R D D . F R P E Y A K I I R D G Y F P Y I Q G LH I L jeo P L I K D E L L Y L S R I Y C E L Q I H K H V A E E . E R E E R L Q Q W F E D H Q . . . S K F P E M E W F E F S A C T G S T L G I F C L V S Y A L R P D . F K P E Y A A V I R E G Y F P Y I Q G LH I L bmq H I V S S H L L E L A N Y Y C D L Q I H K H V E I K . E R V P R L E N W F D A H R . . . H S V P E M E W Y E F S A C S G S T L G I F C L V A Y S F Q E E . M T E E M T Q K I K A G Y F P Y I Q G LH I L beo P L I K S H L L E L C H Y Y C D L Q I H K H V R E E . E R V H R L E T W F H E H Q . . . E K F P N M T W Y E F S A C A G S T L G I F C L V S Y S F Q R D . F T K Q Q A M Q I M S G Y F P Y I Q G LH I L bacy D M I K P Y L L E L C G Y Y C D L Q V H K H V I E H . E R V P R L E K W F T Q Y E . . . S E L P E M E W Y E F S A C A G S T L G I F C L V A Y S F Q P D . F T E S T A K K I R D S Y F P Y I Q G LH I L bsus D M I K P Y L L E L C G Y Y C D L Q V H K H V I E H . E R V P R L E K W F T Q Y E . . . S E L P E M E W Y E F S A C A G S T L G I F C L V A Y S F Q P D . F T E S T A K K I R D S Y F P Y I Q G LH I L balm D M I K P Y L L E L C G Y Y C D L Q V H K H V I E H . E R V P R L E K W F T Q Y E . . . S E L P E M E W Y E F S A C A G S T L G I F C L V A Y S F Q P D . F T E S T A K K I R D S Y F P Y I Q G LH I L bjs D M I K P Y L L E L C G Y Y C D L Q V H K H V I E H . E R V P R L E K W F T Q Y E . . . S E L P E M E W Y E F S A C A G S T L G I F C L V A Y S F Q P D . F T E S T A K K I R D S Y F P Y I Q G LH I L bacl D M I K P Y L L E L C G Y Y C D L Q V H K H V I E H . E R V P R L E K W F T Q Y E . . . S E L P E M E W Y E F S A C A G S T L G I F C L V A Y S F Q P D . F T E S T A K K I R D S Y F P Y I Q G LH I L bae D I I K P Y L L E L C G Y Y C D L Q V H K H V V E H . E R V P R L E N W F T Q F Q . . . A D L P E M E W Y E F S A C A G S T L G I F C L V A Y S F Q P D . F N E D T A K K I R S S Y F P Y I Q G LH I L bacp G I I K P Y L L E L C D Y Y C D L Q V H K H V V E H . E R V P R L K A W F E Q Y R . . . S Q L P E M E W F E F S A C A G S T L G I F C L V A Y S F Q P D . F N E H T A E K I R S S Y F P Y I Q G LH I L bacb G I I K P Y L L E L C D Y Y C D L Q V H K H V V E H . E R V P R L K G W F E Q Y R . . . S Q L P E M E W F E F S A C A G S T L G I F C L V A Y S F Q P D . F N E H T A E K I R S S Y F P Y I Q G LH I L bay G I I K P Y L L E L C D Y Y C D L Q V H K H V V E H . E R V P R L K G W F E Q Y R . . . S Q L P E M E W F E F S A C A G S T L G I F C L V A Y S F Q S D . F N E H T A E K I R S S Y F P Y I Q G LH I L bao G I I K P Y L L E L C D Y Y C D L Q V H K H V V E H . E R V P R L K S W F E Q Y R . . . S Q L P E M E W F E F S A C A G S T L G I F C L V A Y S F Q P D . F N E H T A E K I R S S Y F P Y I Q G LH I L bli D L I K E H L I E L C S Y Y C D L Q V H K H V V E H . E R V P R L E A W F E N Y K . . . S A L P K M E W Y E F S A C A G S T L G I F C L V S Y S V R P D . F T E S M A G K I R D S Y F P Y I Q G LH I L blh D L I K Q H L L E L C S Y Y C D L Q V H K H V V E H . E R V P R L E A W F E N Y R . . . S A L P K M E W Y E F S A C A G S T L G I F C L V S Y S V R S D . F T E S M A G K I R D S Y F P Y I Q G LH I L bgy G L I K E H L L E L C S Y Y C D L Q V H K H V I E H . E R V P R L E A W F D K Y K . . . S A L P E M E W Y E F S A C A G S T L G I F C L V S Y S V R P D . F T E A M A G K I R D S Y F P Y I Q G LH I L bacw P I I Q P Y L H T L C D Y Y S D L Q V H K H V V P H . E R V P R L E S W F R Q Y E . . . K D L P K M E W Y E F S A C A G S T L G I F C L V A Y A L Q P D . F T E K Q A K Q I Y E S Y F P Y I Q G LH I L bpu P I I Q P Y L H T L C D Y Y S D L Q V H K H V V P H . E R V P R L E S W F R Q Y E . . . K D L P K M E W Y E F S A C A G S T L G I F C L V A Y A L Q P D . F T E T Q A K Q I Y E S Y F P Y I Q G LH I L gth D K I M P F L H E L A G Y Y C D L Q V H K H V D V E . E R V P R L E K W F K Q Y K . . . D Q L P P M E W Y E F S A C S G S T L G I F C L V A Y A F A E T . F H E K M A K Q I R D G Y F P Y I Q G LH I L gmc D K I M P F L H E L A G Y Y C D L Q V H K H V D V E . E R V P R L E K W F K Q Y K . . . D Q L P P M E W Y E F S A C S G S T L G I F C L V A Y A F A E T . F H E K M A K Q I R D G Y F P Y I Q G LH I L gwc D K I V P F L H E L A G Y Y C D L Q V H K H V H A R . E R V P R L E N W F K Q Y K . . . D Q L P P M E W Y E F S A C S G S T L G I F C L V A Y A F T E T . F H E E M A K Q I R D G Y F P Y I Q G LH I L gtn E T I V P F L H E L A G Y Y C D L Q V H K H V D T K . E R V L R L E R W F A Q Y K . . . D S L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . M P P E M A K Q V R D G Y F P Y I Q G LH I L gsr E T I V P F L H E L A G Y Y C D L Q V H K H V D T K . E R V P R L E R W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P P E M A K Q V R D G Y F P Y I Q G LH I L gjf E T I V P F L H E L A G Y Y C D L Q V H K H V D T K . E R V P R L E R W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P P E M A K Q V R D G Y F P Y I Q G LH I L gse E T I A P F L H E L A G Y Y C D L Q V H K H V E A S . E R V P R L E K W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P P E M A R Q V R D G Y F P Y I Q G LH I L gct E T I A P F L H E L A G Y Y C D L Q V H K H V E A S . E R V P R L E K W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P P E M A R Q V R D G Y F P Y I Q G LH I L gya E T I A P F L H E L A G Y Y C D L Q V H K H V E A S . E R V P R L E K W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P P E M A R Q V R D G Y F P Y I Q G LH I L gyc E T I A P F L H E L A G Y Y C D L Q V H K H V E A S . E R V P R L E K W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P P E M A R Q V R D G Y F P Y I Q G LH I L gte E T I A P F L H E L A G Y Y C D L Q V H K H V E A S . E R V P R L E K W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P P E M A R Q V R D G Y F P Y I Q G LH I L gka E T I A P F L H E L A G Y Y C D L Q V H K H V E A S . E R V P R L E K W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P P E M A R Q V R D G Y F P Y I Q G LH I L ggh E T I A P F L H E L A G Y Y C D L Q V H K H V E A S . D R V P R L E K W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P P E M A R Q V R D G Y F P Y I Q G LH I L gej E T I A P F L H E L A G Y Y C D L Q V H K H V E A S . D R V P R L E K W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P P E M A R Q V R D G Y F P Y I Q G LH I L gel E T I A P F L H E L A G Y Y C D L Q V H K H V E A S . E R V P R L E K W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P P E M A R Q V R D G Y F P Y I Q G LH I L gea E T I A P F L H E L A G Y Y C D L Q V H K H V E A S . E R V P R L E K W F A Q Y K . . . D A L P P M E W Y E F S A C S G S T L G I F C L V A Y A F G E S . L P L E M A R Q V R D G Y F P Y I Q G LH I L anl H I I A P F L Q E L A G Y Y C N L Q V H K H V K Q E . E R V P R L E R W F E E H K . . . H H L P P M E W Y E F S A C S G S T L G I F C L V A Y A F T D S . F N D E M A L R V R N G Y F P Y I Q G LH I L anm H I I A P F L Q E L A G Y Y C N L Q V H K H V K Q E . E R V P R L E R W F E E H K . . . H H L P P M E W Y E F S A C S G S T L G I F C L V A Y A F T D S . F N D E M A L R V R N G Y F P Y I Q G LH I L aamy D T I A P L L K E L A G Y Y C D L Q V H K H V K Q E . E R I P R L T Q W F A Q H Q . . . N S L P P M E W Y E F S A C S G S T L G I F C L V A Y A F N E S . F S K E M A R R V R D G Y F P Y I Q G LH I L afl E V I A P F L H E L A S Y Y C D L Q V H K H V K K E . E R I P R L K Q W F A K H E . . . A S L P K M E W Y E F S A C S G S T L G I F C L V A Y A C N D A . F D Q L L A Q R V R N S Y F P Y V Q G LH I L agn H I I A P F L H E L A S Y Y C D L Q V H K H V K K E . E R I P R L K Q W F S Q H E . . . A S L P K M E W Y E F S A C S G S T L G I F C L V A Y A C T D S . F D Q R L A E R V R N S Y F P Y V Q G LH I L bby D K I A P V L H E L A C Y Y C D L Q I H K H V K L E . E R E P R L Q K W F E A H K . . . E N L P E M S W F E F S A C A G S T L G I F C L V A Y A F H D E . L H D E D I A K I R Q G Y F P Y V Q G LH I L bce D K I A P V L H E L A C Y Y C D L Q I H K H V K L E . E R E P R L K N W F E A H K . . . E N L P E M S W F E F S A C A G S T L G I F C L V A Y A F H D E . L H D E D I A K I R Q G Y F P Y V Q G LH I L ban D K I A P I L H E L A C Y Y C D L Q I H K H V K L E . E R E P R L Q T W F E A H K . . . E N L P E M S W F E F S A C A G S T L G I F C L V A Y A F H D E . L H D E D I A K I R Q G Y F P Y V Q G LH I L btk D K I A P I L H E L A C Y Y C D L Q I H K H V K L E . E R E P R L Q T W F E A H K . . . E N L P E M S W F E F S A C A G S T L G I F C L V A Y A F H D E . L H D E D I A K I R Q G Y F P Y V Q G LH I L bty D K I A P V L H E L A C Y Y C D L Q I H K H V K L E . E R E P R L K T W F E A H K . . . E N L P E M S W F E F S A C A G S T L G I F C L V A Y A F H D E . L H D E D I A K I R Q G Y F P Y V Q G LH I L bwe D K I A P I L H E L A C Y Y C D L Q I H K H V K L E . E R E P R L K T W F E A H K . . . E N L P P M S W F E F S A C A G S T L G I F C L V A Y A F H D E . L H E E D I V K I R Q G Y F P Y V Q G LH I L bmyc D K I A P I L H E L A C Y Y C D L Q I H K H V K L E . E R E P R L Q T W F E A H K . . . E N V P P M S W F E F S A C A G S T L G I F C L V A Y A F H D E . L L D E D I A K I K Q G Y F P Y V Q G LH I L bcy D K I A P I L H E L A C Y Y C D L Q I H K H V K L E . E R E P R L Q T W F E A H K . . . E S V P P M S W F E F S A C A G S T L G I F C L V A Y A F H D E . L L D E D I I K I K Q G Y F P Y V Q G LH I L far P N I A S E L I G L A Q I Y C D L Q V H K H V V V Q . E R E P R L I S W F G E Y Q . . . S V L P D I T W Y E F S A C A G S T L G I F C L V S Y A F Q G D . F T K E S A K T I T K G Y F P W L Q G LH I L fpn P N I A S E L I G L A S I Y C D L Q V H K H V I V Q . E R E P R L I S W F G E Y Q . . . S V L P D I T W Y E F S A C A G S T L G I F C L V S Y A F Q G N . F T K E S A E T I K K G Y F P W L Q G LH I L sat L A I A P A L H E L A G H Y C E L Q V H K H V R E D . Q R I R R L S S W F R R H Q . . . E H L P P M T W Y E F S A C T G S T L G I F C L I S H A F Q R N . F S R D L P Q L I K K A Y F P W V Q G LH I L len S N L V P V L H E L A S Y Y C D L Q V H K H V T V E . E R V P R L K L W F D L H Q . . . K Q L P E L Y W Y E F S A C A G S T L G I F C L V A Y A F E Q D . L S E S F T N Q V K N S Y F P W V Q G LH I L glj S K V A P T L H E L A S Y Y C E L Q I N K H V K L E . E R I P R L K A W F S L H H . . . K Q F P E L S W Y E F C A C A G S T L G I F C L I S Y S F N Q E . F P E T L T M Q V K N S Y F P W V Q G LH I L npu Q L I A P S L Y H L A D Y Y C D L Q V H K H V Q V K . E R V P R L K A W F E R H R . . . N Q I P Q M K W Y E F S A S T G S T L G I F C L V A Y A S D Q D . C S E E L A T K V K N S Y F P W V Q G LH I L bco K V V K E A N I H L A N L Y S D L Q V H K H V K K E . E R V P R L E K W F A E F E . . . K E V P P M T W Y E F S A S T G S T L G I F C L T A Y S T Y E N . F T E E K A L K V K E G Y F P W V Q G LH I L bse A V I E P E V K E L A K R Y T E L Q I H K H V T P E . E R V P R L T D W F L K Q S G . . D L T D E M K W Y E Y A A S T G S T L G I F T L V A Y A S S D D R L T R E D A K T L Y N G Y F P W L Q G LH I L axl G L I Q E Q L L E L A M K Y I D L Q V D K H V L P E . D R V E R L I K S F E N N S . . . L S D R T I A W Y E Y S A A T G S T L A I F C L I S Y A Y Q K D R L S A T I I S D I Y H G Y F P Y I Q G LH I L tap Q V L Q P Y L L K L S G L Y G D L Q V H K H V A K E . E R I E R L T T W F S H H Q . . . E E H R D L T W Y E F S A C S G S T L G I F C F V S Y G M G M E . L D H Q L A D D I Y Q S Y F P Y M Q G LH I L hhd P M V Q K H T L K L G S L Y T D L Q V H K H V I E E . E R I P R L K S W F K D H Q . . . S E W P H L E W Y E F S A C T G S T L G I F C L V S Y M L N G R . M D E S L A A Q V E R S Y F P F M Q G LH I L vig P T Y Q E Q A L Q L T R L Y S D L Q V H K H V K Q E . E R V P R L T N W S . K E K . . . N C H P . L A W Y E F S A A T G S T L G I F C L M A Y S L A G R . L H R K L A N K I V T A Y F P Y I Q G LH I L lao D V I G G H V L E L E R L Y S D L Q V H K H V K Q E . E R I S R L I N W Y . K E E . . . A D D S S L F W Y E F S A A A G S T L G I F C L V S Y A L N G . . M S A E L A D K I I E S Y F P F V Q G LH I L sje H L V Q L D V A D L S A L Y G E F Q V H K H V K E E . E R V G R M Q Q W H Q R N M . . . S R V P D M Q W Y D F S A S T A S T M G V Y T L V A Y A A G K R . V N R E L V R R V R N C Y F P Y M Q G MH I L tur S L Y A S W L G R L A G L Y V D L Q V Y K H L K V S . E R E V R L I Q L S S Q Q K . . . R L A G D L T W F E F G A A C G S T L G I F T M V A Y A M N Q D . R Y Q I Q P E C I F Q A M F P A V Q E LH I M say S A V A P Y I R T W V N L Y I D L Q V Y K H G P V E . S R V P L L T A W A D R H A D . P R W S . . L E W W E F A A A T G S T L G L F A L A S E A Q A G P S P S P D R I D R L A R L Y F P W M G A LH I L tmr H A V A S P V R R L V A L Y N D L Q V N K H G D Q A . G R L P R L E A W Y H R E A G . . R W H G R L A W W E F A A A C G S T L G V F A L F R E A L L H P A P P A E R V A A L V D A Y F P W I G G LH I L lpil S G L A P R L L P P A A R Y A R M Q A L K H L E P H . R R A A A L A S W A G G E A S . P W P G . . L F W W E F A A S A G S T L G I F A L A A S A G A P P . . . . E Q L D R L E A A Y V P W V T A YH I L aac R T V E S Q V D W Y A R R Y S E L Q E H K H A P A E . E R E H R L L N W S R Q H L A . A Y P G . . V A W H E W A A A T G S T L G M F A L F L A A T E P V T P . . S D V Q K L H Q Q Y F P Y I C G LH I L nth D L V R D D L Y F Y T K L Y T E L Q I Y K H L E L D . K R E S K L K S W H E H Y T T K L N S A G N L Y W W E F A S A S G S T L L I F A L I A L M S K N Y . . D E T S H R S I L N C Y F P W I C G LH I L ctx N L V I T R L K K F I Q M Y S D F M T C S H L D K E . L R N K K I E E W V D R Y Y . . . D K S T G I S K T E I I T A S A S P L L V F V L F A C A H D P Y . L T R E E V D N I W D A Y F P W I C G LH A L clb D V V R D S I S A Y L A L Y I D L Q V T K Y S S N D N E K E V N L I R W S T A H G . . . Q K Y P D L T N W E F C M C I D S G L D I L L L L S L A T N P N . L C E E D A E N I N T A F F P W I S C IH K I Fig. S4. (4/6)

S13 9 3 7 4 5 5 2 2 2 D D D 2 5 0 2 6 0 2 7 0 2 8 0 2 9 0 3 0 0 3 1 0 3 2 0 3 3 0 3 4 0 BalTS L D Y F I D Q E E D I A D D E L N F L F Y Y E N E E Q M I E R F Q Y F V Q K A E E S L S T L P D P K F H R H I W R G I I A I Y L S D E K V Q K . N K E L K K K S K Q M I K M G G L P S L L F Y L NS W I dor L D Y F I D L R E D R E T E Q L N F V S Y Y Q N S G M I Y D R L H L F V E K S L E Q A D R L E Y A K F H Q V V V K G L L A M Y L S D D K S M D . . S D I H F V V K K M L T N S G I G V N L L Y Q LC R Q dmi L D Y F I D L R E D R E T N Q L N F V A Y Y E N P E I V F E R L Q L F V D N S L K Q A E H L E Y A K F H Q V V V Q G L L A M Y L S D E K S M D . . G E I Q S I V K R V I E K C G I G V K L L Y W VC R H dai L D Y F I D L R E D R E T G Q L N F V A Y Y S G S E R I A D R L K L F I H K S Y E A A K T L R Y K K F E R A V V Q G L L A M Y L S D E K G Q D . . R D I R F I T K Q L L T K S G V G V Q V L F W MC C W ddh L D Y F I D L E E D R K T N Q L N F V E Y Y G S K E E Q Q E R L L L F V E T A L N R A R S L K Y P N F H E A I I R G L L A M Y L S D Q K G K S . . G D C G Q V T Q E L I R A G G R P V K V L Y W IC L Q dsy L D Y F I D L E E D R K T N Q L N F V E Y Y A S K K E Q Q E R L L L F V E T A L S Q A R S L R Y P D F H E A I I R G L L A M Y L S D Q K G K S . . R E C G Q V T A E L I R A G G R P V K V L F W IC L Q ddl L D Y F I D L E E D R E T S Q L N F V E Y Y P S P R E R E E R L K H F V E V S Y L Q I R G L N Y P K F H E A I V Q G L M A M Y L S D P K G S S . . Q E C T Q V T Q R L I R A G G I K V K I L Y S IC K R puf L D Y F I D M E E D Q A N G D L N F V S Y Y R N A S Q I L S R L T L F T E Q A F L Q A S T L P N P S F H K T V V Q G L L A M Y L S D P K V A T . . L K D Q S I R K S L L K T A G G Y T R F L Y Y LC K L pft L D Y F I D A A E D Q K S G D L N F V S Y Y Q D S P E T A V H L I H F I Q Q A F L Q A D T L P Y P S F H K T I V Q G L L A M Y L S D P K A N T . . Y Q G . . I K N S L L E T A G G Y T R L L Y L LC K F gfe L D Y F I D L Q E D S S T G D L N F V S Y Y E N F H H K R Q R L L W F L H Q S M D K I S T L D Y P L F H L T V I E G L L S M Y L S D P K T S L . . P E E S L L S K Q L L R A A P P S A T M Y Y Y IC K I toc L D Y Y I D L D E D K D G G D L N F V S Y Y Q N R I K C L E R L K L F Y Q N S L E E S A K L R Y P N F H T T V V D G L M A M Y L S D P K A F T . . G G R E P L T A E L L N R C G F Y A K L M H G FC C R mas L D Y Y I D L Y D D A E N G D L N F V S Y Y N D N Q D C E K H L K R F Y T A S L N A I A R L N E A S F H R M V V D G L L A M Y L S D P K A M A . . N E H L K C S K E I I N T S E N Y A R L L Y R IC K L tpz L D Y L I D Q E E D R R E G D L N F V F Y Y P D A E R G V Q R L S F F L R N A L E R A S G L P D P L F H V T V V R G L P A F Y L S D P K V R D . . Q G L E E A A Y R I L E A G G E E A L R L Y R AC C G dau L D Y F I D Q E E D R Q G G D L N F C F Y Y P D P E T C G R R L R H F L A E S L E R V S R L K R P L F H R T V V K G L L A L Y L S D P K V R R . . Q G L E P V S R M L F A G A G T D A R L M H R VC R A mta L D Y L I D Q E E D R A G G D L N F C A F Y R D G A E A G R R L N Y F L Q E S L V A A R N L P D P A F H L L V V R G L P A F Y L S D G I A S R . . Q E Q L P A R Q A I L R T A G P F S R N L Y R LC R V dku L D Y F I D Q Q E D V E G G D L N F V S Y Y R D G Q Q A A G R L K Y F V D R S L A L A A E L P D P F F H M T V V Q G L L A M Y L S D A K V D E . . Q G L Q A T R C L L L E S G G P A A R R L Y R LC A F slp L D Y L I D Q E E D K L G G D L N F V S Y Y R D E N Q K W E A L R L F V G S S L Q A A S G L R T P S F H R L V V T G L L A M Y L S D P K V R K . . L G Y T P S A L R L M K T A G Q G T L L L Y R IC Q L swo L D Y F I D Q E E D R E G G D L N F T F Y Y A D N R E C I S R L E V F I S Q S H A Q S A R L N D C D F S R V V V E G L L A M Y L S D Q K I A Q . . R Q L Q A A A R Q L L A A S G P N A L K T F Q LC R L blr L D Y L I D L E E D R E G G D L N F V S Y Y Q S D E E A Y E R L Q Y F I E R A K Q S I D Q L P H P A F H R M I V D G L L A F Y L A D Q K V N R Q Q P Q I Y T I S K R L L K K A S S F T S F L F Y VN S L bbe L D Y L I D L E E D K M G G D L N F V S Y Y D S E R I A T E R L K L F I K Q A K A S V K R L P N P A F H R M I V D G L V A F Y L A D R K V N R S Q P H I Y T I A R Q L L K Q A K G L P S V L F Y VN S L pnp L D Y L I D Q E E D A I G G D L N F C S Y Y D N M D K T V E R I A L I V K E A K R T S E R L E H A A F H R M I I E G L L A L Y L S D P K V R K . Q R Q V K R V S R Q L M K D S P . L M R M F F L VN S I pms L D Y L I D Q E E D E A G G D L N F C S Y Y A G M T Q T V E R I A A I V T E A R R R S R R L E H A A F H G M I I E G L L A L Y L S D P K V S K . Q A Q V K Q V S R Q L M K D S P . L M R I F F F VN S L plv L D Y L I D Q E E D L I G G D L N F C S Y Y A D M D E T V N R I A Y F V T K S R E R V A H L D H S H F H R M I I E G L L A L Y L S D P K V K D . Q K Q V R S V S R Q L M K K S P . M T R M F F W MN S I pow L D Y L I D Q E E D R E G G D L N F C R Y Y D S Q E T L V R R I G A I A A N A R R D V R R L P A H R F H R L I I E G L L A L Y L S D P K V R S . Q A D V R R V S R L L L R N S P . M T R L F L L VN S K pbj L D Y L I D Q E E D R V G G D L N F C N Y Y D N S S H V V Q R I G D I V R L A R Q D V T K L P N D R F H R L I I E G L L A L Y L S D P K V S G . Q E D V R R V S R S L M K N S P . A T R M F F F LN S V pjd L D Y L I D Q E E D R A G G D L N F C H Y Y D S Q Q Q L V E R I V T I V N R A R D D V K K L P A A G F H R L I I E G L L A L Y L S D P K V R T . Q S D V L A A S R K L M K N S P . L T R L F F W VN S I pdu L D Y L I D Q D E D R A G G D L N F C N Y Y D N T D I M L N R I A S I V E W A R R D V R N I P E T P L H R M V I E G L L A L Y L S D P K V S E . Q R E V R S V S R R L M K R S P . L T R L F F F VN S R psab L D Y L I D Q D E D R A G G D L N F C N Y Y D N T D T M L N R I A S I V E W A R N D V R N I P E T P L H R M V I E G L L A L Y L S D P K V S E . Q R E V R S V S R R L M K R S P . L T R L F F F VN S R pste L D Y L I D Q D E D R A G G D L N F C N Y Y D S T E T M L N R I A S I V E W A R K D V R N I P D T P L H R M V I E G L L A L Y L S D P K V S E . Q R E V R T V S K K L M K R S P . L T R L F F F AN S R paee L D Y L I D Q D E D R A G G D L N F C N Y Y D N T D T M L N R I A S I V E W A R K D V R S L P E N S M H R M V I E G L L A L Y L S D P K V S E . Q R E V R T V S K R L M K R S P . L T R L F F F VN S R paea L D Y L I D Q D E D R A G G D L N F C N Y Y D N T D T M L N R I A S I V E W A R K D V R S L P E N S M H R M V I E G L L A L Y L S D P K V S E . Q R E V R T V S K R L M K R S P . L T R L F F F VN S R paeq L D Y L I D Q D E D R A G G D L N F C N Y Y D N T D T M L N R I A S I V E W A R K D V R T L P E T S M H R M V I E G L L A L Y L S D P K V S E . Q R E V R S V S K R L M R K S P . L T R L F F F VN S R paen L D Y L I D Q D E D R A G G D L N F C N Y Y D D T D T M L N R I A S I V E W A R K D V R T L P E T S M H R M V I E G L L A L Y L S D P K V S E . Q R E V R S V S K R L M R K S P . L T R L F F F VN S R pbd L D Y L I D Q D E D R A G G D L N F C N Y Y D N T D T M L N R I A S I V E W A R K D V R N L P E T S M H R M V I E G L L A L Y L S D P K V S E . Q R E V R S V S K R L M R K S P . L T R L F F F VN S R paeh L D Y L I D Q D E D R A G G D L N F C N Y Y D N S D T M L N R I A S I V E W A R K D V R N L P E T S M H R M V I E G L L A L Y L S D P K V S E . Q R E V R T V S K R L M R K S P . L T R L F F F VN S R pgm L D Y L I D Q D E D R A G G D L N F C N Y Y D T S D T M L N R I A S I V E W A R R D V R N L P E T S M H R M V I E G L L A L Y L S D P K V S E . Q R E V R S V S R R L M R R S P . L T R L F F F VN S R pri L D Y L I D Q D E D R A G G D L N F C N Y Y D T S D T M L N R I A S I V E W A R R D V R N L P E T S M H R M V I E G L L A L Y L S D P K V S E . Q R E V R S V S R R L M R R S P . L T R L F F F VN S R paej L D Y L I D Q E E D R A G G D L N F C N Y Y D D T D T M L S R I A S M V E W A R K D V R E L P E S S M H R M V I E G L L A L Y L S D P K V S E . Q R E V R T V S K S L M R G S P . L T R L F F F AN S R paef L D Y L I D Q E E D R A G G D L N F C N Y Y D D T D T M L S R I A S M V E W A R K D V R E L P E S S M H R M V I E G L L A L Y L S D P K V S E . Q R E V R T V S K S L M R G S P . L T R L F F F AN S R pod L D Y L I D Q E E D R A G G D L N F C N Y Y D D T D T M L S R I A A M V E W A R K D V R N L P E S S M H R M V I E G L L A L Y L S D P K V S E . Q R E V R S V S K S L M K G S P . L T R L F F F AN S R gym L D Y L I D Q D E D R L G G D L N F C N Y Y E D A D T M L N R I A S I V E W A R K D V R T I P S T P F H R M I I E G L L A L Y L S D P K V S E . Q Q L V R T V S K R L M K K S P . M T R I F F Y VN S R ppeo L D Y L I D Q D E D R K G G D L N F C N Y Y E D T D M M L D R I A Y V V N R A R A D I A D V P A S S F H R M I I E G L L A L Y L S D P K V S E . Q Q D V R A V S R R L M K N S P . L M R L F F L LN S R ppy L D Y L I D Q D E D R K G G D L N F C N Y Y E D T D M M L D R I A Y V V N R A R A D I A D V P A S S F H R M I I E G L L A L Y L S D P K V S E . Q Q D V R A V S R R L M K N S P . L M R L F F L LN S R pta L D Y L I D Q D E D R K G G D L N F C N Y Y E D T D M M L N R I A Y V V N R A R V D V A D V P A S S F H R M I I E G L L A L Y L S D P K V S E . Q Q E V R A V S K R L M K N S P . L M R L F F F LN S R pih L D Y L I D Q E E D R V G G D L N F C N Y Y K D S E T L L D R I A F I V E S A R E D V A N I P S P S F H R L I I E G L L A I Y L S D P K V R E . Q Q E V R S I S K R L M R K S P . W T R L F F F MN S R pbv L D Y V I D Q E E D R R G G D L N F C N Y Y D S P D T M Y E R I E Q I V D W A R R D V N T I P G T S F H R M I I E G L V A L Y L S D P K V S E . Q Q E V R T V S R R L M R K G P . L T R V F F M VN S R tco L D Y L I D Q E E D R L G G D L N F C S Y Y E N D A E M L Q R I G W I A D Q A R K A A C R L P S N K F H K M V I E G L L A V Y L S D P K A A E . Q P V V R F V A R E L M R N S P . M A R L F F R LN V L anx L D Y L I D L E E D E I G G D L N F I A Y Y Q N E R E I Y E R I H Y I V G E A K K N I Q A L P D R K F H N M I V D G L L G L Y L S D G K V Q R . Q P M V R R V A R W I L R S S S . L P T R F F F LN S R bpf L D Y F I D Q E E D I A D D E L N F L F Y Y D S E E E M I E R F R Y F V K K A E E S L S T L P D P K F H R L I Y Q G I I A I Y L S D E K V Q G . N K E M K K K S K K M I K T G G L P T F I F Y L NS W V bha L D Y F I D Q E E D I A D D E L N F L F H Y Q N E E E M I E R F R Y F L A R A E E T M A E L P D P K F H R M I H R G L I A I Y L S D D K V Q K . H P K Y K R Q S K R M I K M G G L P T F L F Y L NS W M bcl L D Y F I D Q E E D R Q E N E M N F V A Y Y G D S K E M F E R F K Y I D Q K A T E K L Q M L P D K K F H L L L K T G L Y A L Y L S D K K V M S . H P R L K A E A K Q L I K L G G F P A S L F Y Y NR W I ble L D Y F I D Q E E D R L E N E M N F A A Y Y E S K E D M M E R F R F L D E Q A N L K L K G L P D E K F H M L L K K G L Y A L Y L S D G K V A N . N P E L K K D A K E I I K L G G K S A A F F F Q NR W M bmet L D Y F I D Q E E D L A G G D L N F C F Y Y D N Q E K L F N R L K H F I E E A D R H T E K L P N K R F H K L I N R G L L G V Y L S D E K V R K . Q K N I R K L A R E L I K K G G S I S L F F Y L NG R A gst L D Y F I D Q E E D V V G G D L N F C F Y Y D S Q E I L C N R L K Y F V S E A D R H T E L L P H K K F H Q L I N R G L L G I Y L S D S K V R K . Q K D V R K L A K E I I K S G G W I S Y F F Y L NG V V baci L D Y F I D Q E E D R L G G D L N F C F Y Y E N K Q T L F N R L K Y F L L E A D R H T K K L P N Q K F H R L I N R G L L G I Y L S D K K V A K . Q K G V R K L A K E I I K T G G A V S Y F F Y V NG L I bif L D Y L I D Q E E D L E G G D L N F C F Y Y Q D E Q Q L F A R L Q H F I A E A D K H I E G L P H K S F H R L I N R G L L G I Y L S D E K V R R . Q K H V R R L A R H I I K T G G P V S Y F F Y V NG R A bsm L D Y F I D Q E E D R K G G D L N F C F Y Y D S Q E E L L S R F Q Y F I Q K A D S S T K H L P H A K F H Q L I N R G L L G I Y L S E D K V N Q . Q K D V Q S L A K K I I R F G G S T S Y F F Y Y NG R M bck L D Y F I D Q D E D K K G G D L N F C F Y Y P G E E E L F K R L K H F L Q E A D K H T A R L P N E K F H K L I N R G L L A V Y L S D E K V R K . Q R S V Q K L S R K M I K F A G S I S L F F Y V NG K M jeo L D Y F I D Q E E D K E E G D L N F C F Y Y K N P E N L F K R L Q H F I R E A D R H T R K L P H S R F H M L I N R G L L G V Y L S D D K V N S . Q K K V R D L A R K M I R S S G A V S F F F Y M NG R A bmq L D Y L I D Q E E D K A G G D L N F C F Y Y P H Y Q Q M M D R F L H F V V K A D E Y A K K L P D Y H F H C F I Y K G L L G V Y L S D Q K V R A . Q K H V H V N A R R L I K A G G A L S Y F F Y I NG R L beo L D Y F I D Q E E D K E E G D L N F C F Y Y P E Q E E M M K R F Y H F V S E A D K K I K G L P H E H F H H F I N R G L L G L Y L S D R K V K K . Q R N V H K Q A K K I I K L G G K I S R F F Y W NG R L bacy L D Y L I D Q E E D L L E G D L N F C S Y Y Q S H E E M M D R L E H F I H K A D E H L Q G I P H E N F H R L I N R G L L G V Y L S D D K V A G . Q K E M G R L A K K L I K A S G K T S L F F Y I NG R A bsus L D Y L I D Q E E D L L E G D L N F C S Y Y Q S H E E M M D R L E H F I H K A D E H L Q G I P H E N F H R L I N R G L L G V Y L S D D K V A G . Q K E M G R L A K K L I K A S G K T S L F F Y I NG R A balm L D Y L I D Q E E D L L E G D L N F C S Y Y Q S H E E M M N R L E H F I H K A D E H L Q G I P H E N F H R L I N R G L L G V Y L S D D K V A G . Q K E M G R L A K K L I K A S G K T S L F F Y I NG R A bjs L D Y L I D Q E E D L L E G D L N F C S Y Y Q S H E E M M N R L E H F I H K A D E H L Q G I P H E N F H R L I N R G L L G V Y L S D D K V A G . Q K E M G R L A R K L I K A S G K T S F F F Y I NG R A bacl L D Y L I D Q E E D L L E G D L N F C S Y Y Q S H E E M M D R L E H F I H K A D E H L Q G I P H E N F H R L I N R G L L G V Y L S D D K V A G . Q K E M G R L A K K L I K A S G K T S L F F Y I NG R A bae L D Y L I D Q E E D L L G G D L N F C T Y Y E S H E E M M K R L E H F I E K A D E H L R G I P H E S F H R L I N R G L L G V Y L S D D K V A G . Q K E M G R L A K K L I K A S G K T S F F F Y I NG R A bacp L D Y L I D Q E E D L L E G D L N F C T Y Y Q S H E E M M Q R L Q H F I E K A D E H L Q G I P H E N F H R L I N R G L L G V Y L S D D K V A G . Q K E M G R L A R K L I R A S G K T S F F F Y I NG R A bacb L D Y L I D Q E E D L L E G D L N F C T Y Y Q S H E E M M Q R L Q H F I E K A D E H L K G I P H E N F H R L I N R G L L G V Y L S D D K V A G . Q K E M G R L A R K L I R A S G K T S F F F Y I NG R A bay L D Y L I D Q E E D L L E G D L N F C T Y Y Q S H E E M M Q R L Q H F I E K A D E H L Q G I P H E N F H R L I N R G L L G V Y L S D D K V A G . Q K E M G R L A R K L I R A S G K T S F F F Y I NG R A bao L D Y L I D Q E E D L L E G D L N F C T Y Y Q S H E E M M Q R L K H F I E K A D E H L H G I P H E N F H R L I N R G L L G V Y L S D D K V A S . Q K E M G R L A R K L I R A S G K T S F F F Y I NG R A bli L D Y L I D Q E E D L I G G D L N F C T Y Y P S H S D M M E R L E Y F I E M A D E H L R G I P H E N F H R L I N R G L L G V Y L S D D K V A G . Q K E I G R L A K K L I K A S G K T S F F F Y I NG R A blh L D Y L I D Q E E D L I G G D L N F C T Y Y P S H S D M M E R L E Y F I E M A D E H L R G I P H E N F H R L I N R G L L G V Y L S D D K V A G . Q K E I G R L A K R L I K A S G K T S Y F F Y I NG R A bgy L D Y L I D Q E E D L I G G D L N F C T Y Y S S H S E M M E R L E H F I E M A D E H L R G I P H E N F H R L I N R G L L G V Y L S D D K V A G . Q K E I G R L A K K L I K A S G K T S F F F Y I NG R A bacw L D Y L I D Q E E D R L G G D L N F C S Y Y D S H H E M M D R L Q H F I E K A D E Q L K G I P H E N F H K L I N R G L L A V Y L S D E K V T A . Q K E M N K L A K R L I K S S G K T S F F F Y I NG R A bpu L D Y L I D Q E E D R L G G D L N F C S Y Y A S H H E M M N R L Q H F I E K A D E Q L K G I P H E N F H K L I N R G L L A V Y L S D E K V T A . Q K E M N K L A K R L I R S S G K T S F F F Y I NG R A gth L D Y F I D Q E E D R Q E G D L N F C F Y Y P N Q S V L L E R F C H F I E E A D R H V S E L P H G A F H R L I H R G L L G L Y L S D E K V K K . Q K E L R R L A K R L I R A G G I V S W F F Y W NG K A gmc L D Y F I D Q E E D R Q E G D L N F C F Y Y P N Q S V L L E R F C H F I E E A D R H V S E L P H G A F H R L I H R G L L G L Y L S D E K V K K . Q K E L R R L A K R L I R A G G I V S W F F Y W NG K A gwc L D Y F I D Q E E D R L G G D L N F C F Y Y P N Q S V L L E R L C H F I E E A D R H V N Q L P H G E F H R L I H R G L L G L Y L S D E K V K K . Q K E L R R L A K K L V R S G G M I A W F F Y W NG K A gtn L D Y L I D Q E E D R E G G D L N F C F Y Y P N E T V L L E R L C H F I E E A D R H V G T L P H G K F H R L I H R G L L G L Y L S D E K V K K . Q R A L R R L A R Q L V R A G G A A S Q F F Y W NG K A gsr L D Y L I D Q E E D R E G G D L N F C F Y Y P N E T V L L E R L C H F I E E A D R H V G E L P H G E F H R L I H R G L L G L Y L S D D K V K K . Q R G L R R L A R Q L V R A G G A A S Q F F Y W NG K A gjf L D Y L I D Q E E D R E G G D L N F C F Y Y P D E T V L L K R L C H F I E E A D R H V G A L P H G E F H R L I H R G L L G L Y L S D D K V K K . Q E R L R R L A R R L V R A G G A A S M F F Y W NG K A gse L D Y L I D Q E E D R D G G D L N F C F Y Y P N E T V M L E R L C H F I E E A D R H V G A L P H G E F H R L I H R G L L G L Y L S D A K V K K . Q R G L R R L A R R L V R A G G A A S Q F F Y W NG K A gct L D Y L I D Q E E D R D G G D L N F C F Y Y P N E T V M L E R L C H F I E E A D R H V G A L P H G E F H R L I H R G L L G L Y L S D A K V K K . Q R G L R R L A R R L V R A G G A A S Q F F Y W NG K A gya L D Y L I D Q E E D R D G G D L N F C F Y Y P N E T V M L E R L C H F I E E A D R H V G A L P H G E F H R L I H R G L L G L Y L S D A K V K K . Q R G L R R L A R R L V R A G G A A S Q F F Y W NG K A gyc L D Y L I D Q E E D R D G G D L N F C F Y Y P N E T V M L E R L C H F I E E A D R H V G A L P H G E F H R L I H R G L L G L Y L S D A K V K K . Q R G L R R L A R R L V R A G G A A S Q F F Y W NG K A gte L D Y L I D Q E E D R D G G D L N F C F Y Y P N E T V M L E R L C H F I E E A D R H V G A L P H G E F H R L I H R G L L G L Y L S D A K V K K . Q R G L R R L A R R L V R A G G A A S Q F F Y W NG K A gka L D Y L I D Q E E D R D G G D L N F C F Y Y P N E T V M L E R L C H F I E E A D R H V G A L P H G E F H R L I H R G L L G L Y L S D A K V K K . Q R G L R R L A R R L V R A G G A A S Q F F Y W NG K A ggh L D Y L I D Q E E D R D G G D L N F C F Y Y P N E T V M L E R L C H F I E E A D R H V G A L P H G E F H R L I H R G L L G L Y L S D A K V K K . Q R G L R R L A R R L V R A G G A A S Q F F Y W NG K A gej L D Y L I D Q E E D R D G G D L N F C F Y Y P N E T V M L E R L C H F I E E A D R H V G A L P H G E F H R L I H R G L L G L Y L S D A K V K K . Q R G L R R L A R R L V R A G G A A S Q F F Y W NG K A gel L D Y L I D Q E E D R A G G D L N F C F Y Y P N E T V M L E R L C H F I E E A D R H V G A L P H G Q F H R L I H R G L L G L Y L S D A K V K K . Q R G L H R L A R R L V R A G G A A S M F F Y W NG K A gea L D Y L I D Q E E D R A G G D L N F C F Y Y P N E T V M L E R L C H F I E E A D R H V G A L P H G Q F H R L I H R G L L G L Y L S D A K V K K . Q R G L H R L A R R L V R A G G A A S M F F Y W NG K A anl L D Y F I D Q E E D R N G G D L N F C F Y Y P N D A A L F E R L C H F I E E A D R H V E E L P H G A F H R L I H R G L L G L Y L S D G K V N E . Q R E V Q R L A K R L I R C G G A I S H F F Y W NG R M anm L D Y F I D Q E E D R N G G D L N F C F Y Y P N D A A L F E R L C H F I E E A D R H V E E L P H G A F H R L I H R G L L G L Y L S D G K V N E . Q R E V Q R L A K R L I R C G G A I S H F F Y W NG R M aamy L D Y F I D Q E E D R L G G D L N F C F Y Y P N D I V L L E R L C H F I E E A E R R L L E L P H G A F H R L I H R G L L G L Y L S D E K A R A . H P N M R R L A K Q L L R A G G S I S R F F Y W NG R M afl L D Y F I D Q E E D R Q G G D L N F C F Y Y P N E E T L F A R L R H F I E E A D R H I A Q L P H R E F H R F I H R G L L G L Y L S D E K V H E . Q E T I R K L A K Q L L R S G G M T S H F F Y W NG R M agn L D Y L I D Q E E D R Q G G D L N F C F Y Y P N E E T L F A R L C H F V E E A D R H I A Q L P H R E F H R F I H R G L L G L Y L S D E K V H E . Q N A I R K L A K Q L L R S G G I T S H F F Y W NG R M bby L D Y F I D Q E E D R I G G D L N F C S Y Y E N E Q A I L D R M K H F V E E A E K S I G D L P H A K F H R L I S R G L L G I Y L S D Q K V S A . Q K N M H K M A R R I V K Y G G L T S R F F Y W NG K M bce L D Y F I D Q E E D R I G G D L N F C S Y Y E N E Q A I L D R M K H F V E E A E K S I G D L P H A K F H R L I S R G L L G I Y L S D Q K V S A . Q K N M H K M A R R I V K Y G G L T S R F F Y W NG K M ban L D Y F I D Q E E D R I G G D L N F C S Y Y E N E Q V I L D R M K H F V E E A E K S I G D L P H A K F H R L I S R G L L G I Y L S D Q K V S A . Q K N M H K M A R R I V K Y G G L T S R F F Y W NG K M btk L D Y F I D Q E E D R I G G D L N F C S Y Y E N E Q V I L D R M K H F V E E A E K S I G D L P H A K F H R L I S R G L L G I Y L S D Q K V S A . Q K N M H K M A R R I V K Y G G L T S R F F Y W NG K M bty L D Y F I D Q E E D R I G G D L N F C S Y Y E N E Q A I L D R M K H F V E E A E N S I G D L P H A K F H R L I S R G L L G I Y L S D Q K V S A . Q K N M H K M A R R I V K Y G G L T S R F F Y W NG K L bwe L D Y F I D Q E E D R I G G D L N F C S Y Y E N E Q A I L D R M K H F V E E A E K S I G D L P H A K F H R L I S R G L L G I Y L S D Q K V S A . Q K N M H K M A R R I V K Y G G L T S R F F Y W NG K M bmyc L D Y F I D Q E E D R L G G D L N F C S Y Y E N E Q V V L E R M K H F V E E A E R N I D G L P H A K F H R L I S R G L L G I Y L S D Q K V S E . Q K N M Q Q M A R R I V K Y G G F T S R F F Y W NG K M bcy L D Y F I D Q E E D R I G G D L N F C S Y Y E N E Q V I L A R M K H F V Q E A E K S I S D L P H A K F H R L I S R G L L G I Y L S D Q K V L E . K K N M Q H I A R R I V K Y G G F T S R F F Y W NG K M far L D Y F I D Q N E D K L E G D L N F C T Y Y K N E Q H M L E R M V Y F A K E A E S S C S K L P N S K F H R L I Q R G L L G I Y L A D R K V S E . C P V I K K M A S Q L V K V G G A T S Y F F Y V NR K V fpn L D Y F I D Q N E D K L E G D L N F C T Y Y K N D Q H M L E R M V Y F A E R A E K S C A N L P N S R F H R L I Q R G L L G I Y L A D R K V S E . S P G I K K M A A K L V K V G G A T S Y F F Y V NR K L sat L D Y L I D Q E E D R Y G G D L N F C S F Y P T T A E L E K R L T H F Y T S A D K S I A H L P Y A S F H R L I N R G L L G I Y L A D R K V D C . Q K E V R K I A R R M I R H G G G I A F F F F L HC L I len L D Y L I D Q E E D R I H G D L N F C F Y Y N S Q E Q M L D R F K H F V D N A K R S V S Q L P H A Q F H Q L I N Q A L L G V Y L S N K K V R G . Q R E V Q T I A K Q L I A I G G R P A S F F F R SR L L glj L D Y L I D Q E E D R M N N D L N F C F Y Y S S E D E L T A R L Q Q F V E E A T K S V A S L P H S Q F H Q L I P Q A L L G V Y L S S E K V S K . Q G A V Q K I A T R L I P D G S . P A S F F F Q QG L L npu L D Y F I D Q E E D R I G G D L N F C A Y Y N N G Q E I S E R F A Y F L K Q A D K A V S R L P H D R F H R M I N R A L L G V Y L A D E K V N Q . Q E N I K E T A K K I L S S C G G S S L F F M W NI M I bco M D Y F I D Q E E D R L G G D L N F C F Y Y K D E E E M M D R L V H F F R Q A D K S I R D L P D W K F H R L I N N G L L A I Y L A D E K V K Q . D P H L R K Q G H R F I R S G G A P T M F F Y V NG W L bse M D Y F I D Q E E D R V E G D L N F C A Y Y K D D Q A M L E G I G R F Y R M A K D A I Q T L P D R R F H R M I T S G L I A I Y L S D P K V R H . H P L L R K Q Q L K L I Q F G G P Q T I F F Y L NG R Y axl L D Y L I D Q E E D R L E N D L N F C F Y Y P S H E E M E Q R I V Y F I D Q S K K S V R H L P D D H F H R Y I Y E G L L A L Y L A D P K V H T . I K D G Q R L K R R L L K A G G Y R A R F F H W GI R F tap L D Y Y I D Q M E D E E E G D L N F C H Y Y R D A E E M R E R L L Y F I E R T N E S V Q R L P H A S F H E M V H H G L V G L Y L A D S K V S L . L S D G K Q M I K T L L K A S G N K S K F F H L NI K A hhd L D Y Y I D Q R E D E E E G D L N F C S Y Y A H E E Q M K H R F E Y F V R Q T H E E V Q E L P D T A F H Q M I H E G L V G M Y L A D R K V G K . L D N A K S F V K D L L K V S G R K A K F F Y Y NT K M vig L D Y Y I D Q Q E D K E E G D L N F C S Y Y E S Q T V M H E R F Q Y F C E Q A K V Y A G T I P N P S F H K M V V Q G L V G L Y L G D G K V N H . I N D S T P F K Q L L F Q T A G K P A M F F Y R NT R I lao L D Y Y I D Q E E D R V E G D L N F C S Y Y D N P E L M Q K R F M Y F I E Q A D H Q V Q Q L P D R R F H E M V H H G L V G L Y L G D P K T K K . L D G G M T I T D N L L Q I S G Y K A R F F H W NT K L sje L D Y Y I D Q A E D E A D G E M N F C T Y Y P S N E A L K K R I G E F M E E T D R K I A E L P D A D F H Q M L R E G V V S M Y L A D E K V K E . L P G S S S M V P Y L L N K S G T R S W F F Y L NV K A tur L D Y L I D L E E D I E E G E L N F F S Y Y H N F E E G I Y R I L D V Y Y E A Q Q Q I R L L P E K G F H Q T I N D G L F A L Y L A E G . V K K . N P K L R I V Q K Q I I K K L G F R A R F L F H HT R K say L D Y W I D Q Q E D A Q G G D L N F V T Y Y P S Q K E A L K R I Q W I F D E A L A A S T L L E D A A F H H Y I A R G L L G F Y L A D . Q K A R . . Q G L R S P S C R L L V Q G G P L S V G V W L VS L V tmr L D Y L I D Q A E D R A G G D L N L V R P Y G D P S R A V E G L A A F A R E A A R R A E A L P D A P L H R L V V D G L L G L Y L T D P K V A R . . Q H L Q P V A R R L L A A G G P G A R M C F A AS R F lpil L D Y L I D L D E D R A G G D L N F V A C Y P S L D V A A R R L R A L A G Q A R R R I E A L E A P A F H R L V V H G L T G L Y L A D A K A R A . . P M L R P V A A T L L D E A G S D A R A L A W LC R W aac L D Y W I D A L E D E A H G D F N F V A C Y R D P A S A W E R I E Q F A A E G V E R A A D I P G G V I H R Y V V H G L M G M Y L S D P K T R S . . A A H L T A S R R R I Y R F G V T P I L F Y Y AT H L nth L D Y L I D Q E E D Y R E Q D L N F V F F Y P N K E M M L T R L K Y F V N K S L E S I K E L P N A D F H K M V V K G L L A L Y L S D P K I E S . . Q G M E L L R N D L L S T G G S D T L M L Y K VC K S ctx L Y N F V N V N . D V F G N N N N L A F Y Y K N L K M Y E D K I T F F I E K S L E S C N K L K Y P E F H R T A V K M I I A L Y L S N P Q A Y H . . G M N R L A S T N I M K K S G S A A R F Y Y N LC K L clb L E C Y L K Y N D D L S S G S L N Y V F Y Y G S L K E Y E D R I K F F T D K A L S V R T G Y R S N . . I K S V L K I L L S L F I T D P K A S E . . G M N K I T S K G L Y K S G G K G M W L Y A L SA K I Fig. S4. (5/6)

S14 3 5 0 BalTS Y R R D K ...... dor L R R G K V I ...... dmi L R K R K I I ...... dai L R K R N L L ...... ddh L R K K G R L ...... dsy L R K K G K L ...... ddl L R G K G M L ...... puf L R F K K K L ...... pft L R F R K K L ...... gfe L R R N N I I ...... toc L R K T A R L ...... mas I R R R G S L ...... tpz L R R Q G K I ...... dau L R R V G V V ...... mta L R R A G V V ...... dku L R K V G I V ...... slp V R R A K Q V ...... swo V R K I F ...... blr F I R R K E T ...... bbe L V R R ...... pnp W I R K N S ...... pms W I R R T S Q A ...... plv W I R K T S ...... pow W I R I R N V ...... pbj W I R R R K A ...... pjd W I R R Q Q V ...... pdu W I R K H L Y ...... psab W I R K H L Y ...... pste W I R K H L Y ...... paee W I R K H M Y ...... paea W I R K H M Y ...... paeq W I R K H M Y ...... paen W I R K H M Y ...... pbd W I R K H M Y ...... paeh W I R K H M Y ...... pgm W I R R H M Y ...... pri W I R R H M Y ...... paej W I R N R F L ...... paef W I R N R F L ...... pod W I R K R F L ...... gym W I R K H K H E ...... ppeo W I R R L I ...... ppy W I R R L I ...... pta W I R R L L ...... pih W I R K H L Y K ...... pbv W I R K Y M Y E H ...... tco W I R R R A K P P R ...... anx G Y R G G K A V L Q A P P S G K . . . . . bpf F R R S ...... bha F R R K S G E Q P A M D S M ...... bcl F K R K I S ...... ble F K R A I ...... bmet Y R A M Q K W M P L G L M K ...... gst Y R S L Q K S V P S L M E R M L I T K . . baci F R R V E K L V P A G V I R A L V K . . . bif Y R T V Q K W V P A G L A R L L F . . . . bsm Y R K F R Q H V S K ...... bck Y R A I K N M I P A S L A K T I V K . . . jeo Y R N V M R F L S G N P Y I K S Q V . . . bmq Y R M L K R ...... beo Y R I L Q K S T P H ...... bacy Y R K F Q K M S W M K N S K K K A Q I I C bsus Y R K F Q K M S W M K N S K K K A Q I I C balm Y R K F Q K M S W M K N S K K K A Q I I C bjs Y R K F Q K M S W M K N S K K K A Q I I C bacl Y R K F Q K M S W M K N S K K K A Q I I C bae Y R K F Q K M P W M R S S ...... bacp Y R K F Q K M A W T K S S ...... bacb Y R K F Q K M A W T K S S ...... bay Y R K F Q K M A W T K S S ...... bao Y R K F Q K M A W T K S S ...... bli Y R K I Q K M P W M K S S ...... blh Y R K I Q K M P W M K S S ...... bgy Y R K I Q K M P W M K S S ...... bacw Y R T Y Q K M P W M K S S ...... bpu Y R T Y Q K M P W M K S S ...... gth Y R L W Q K K R S S I A K ...... gmc Y R L W Q K K R S S I A K ...... gwc Y R L W Q K K F S V I A K ...... gtn Y R F W Q E K Q K R L S F S ...... gsr Y R F W Q E K Q K R L S F S ...... gjf Y R F W Q E Q Q K R L S L S ...... gse Y R F W Q E R Q K R L S F S ...... gct Y R F W Q E R Q K R L S F S ...... gya Y R F W Q E R Q K R L S F S ...... gyc Y R F W Q E R Q K R L S F S ...... gte Y R F W Q E R Q K R L S F S ...... gka Y R F W Q E R Q K R L S F S ...... ggh Y R F W Q E R Q K R L S F S ...... gej Y R F W Q E R Q K R L S F S ...... gel Y R F W Q E R Q K R L S F S ...... gea Y R F W Q E Q Q K R L S F S ...... anl Y R A W Q K W A K ...... anm Y R A W Q K W A K ...... aamy Y R A W Q K W A ...... afl Y R K W Q R W M Y A ...... agn Y R K W Q K W M Y A ...... bby Y R K K T A Q ...... bce Y R K K T A Q ...... ban Y R K K T A Q ...... btk Y R K K T A Q ...... bty Y R K K M A Q ...... bwe Y R K K M A Q ...... bmyc Y R K K M A Q ...... bcy Y R K K M A Q ...... far Y Q K L K P S L S ...... fpn Y Q R L K P S L S ...... sat Y R R I H E K Q D P V P P S D S . . . . . len L S H ...... glj A S H S T Q ...... npu M A Q I R Y R K I L A ...... bco Y R R A S G T ...... bse I H K K ...... axl L N R H I K T T D Q I F ...... tap Y N K M K E A R T P V S ...... hhd Y H K L K P G R P L ...... vig Y Y F F K Q F I H ...... lao Y H R M T K T R N ...... sje Y H K L K A ...... tur F V K ...... say G R A P ...... tmr V R R W R G N A G ...... lpil R N P F G Q V A E P Q P P P A R . . . . . aac Y R R M A ...... nth L R R V G V I ...... ctx L R L S G K F ...... clb L R F L N K F ......

Fig. S4. (6/6)

S15 Fig. S4. Sequence alignment of BalTS homologue proteins. Several residues including the characteristic aspartates in the two motifs are indicated over the alignment. These panels were prepared using ESPript.25 Abbreviations; dor: Desulfosporosinus orientis, dmi: Desulfosporosinus meridiei, dai: Desulfosporosinus acidiphilus, ddh: Desulfitobacterium dehalogenans, dsy: Desulfitobacterium hafniense Y51, ddl: Desulfitobacterium dichloroeliminans, puf: Pelosinus sp. UFO1, pft: Pelosinus fermentans, gfe: Geosporobacter ferrireducens, Thermosediminibacter oceani, mas: Mahella australiensis, tpz: Thermacetogenium phaeum, dau: Candidatus Desulforudis audaxviator, mta: Moorella thermoacetica, dku: Desulfotomaculum kuznetsovii, slp: Syntrophothermus lipocalidus, swo: Syntrophomonas wolfei, blr: Brevibacillus laterosporus, bbe: Brevibacillus brevis, pnp: Paenibacillus naphthalenovorans, pms: Paenibacillus mucilaginosus KNP414, plv: Paenibacillus larvae, pow: Paenibacillus sp. 32O-W, pbj: Paenibacillus beijingensis, pjd: Paenibacillus sp. JDR-2, pdu: Paenibacillus durus, psab: Paenibacillus sabinae, pste: Paenibacillus stellifer, paee: Paenibacillus sp. FSL R7-0331, paea: Paenibacillus sp. FSL R7-0273, paeq: Paenibacillus sp. FSL R5-0912, paen: Paenibacillus sp. FSL P4-0081, pbd: Paenibacillus borealis, paeh: Paenibacillus sp. FSL H7-0357, pgm: Paenibacillus graminis, pri: Paenibacillus riograndensis, paej: Paenibacillus sp. FSL H7-0737, paef: Paenibacillus sp. FSL R5-0345, pod: Paenibacillus odorifer, gym: Paenibacillus sp. Y412MC10, ppeo: Paenibacillus peoriae, ppy: Paenibacillus polymyxa E681, pta: Paenibacillus terrae, pih: Paenibacillus sp. IHBB 10380, pbv: Paenibacillus bovis, tco: Thermobacillus composti, anx: Aneurinibacillus sp. XH2, bpf: Bacillus pseudofirmus, bha: Bacillus halodurans, bcl: Bacillus clausii, ble: Bacillus lehensis, bmet: Bacillus methanolicus, gst: Bacillus sp. X1(2014), baci: Bacillus sp. 1NLA3E, bif: Bacillus infantis, bsm: Bacillus smithii, bck: Bacillus coagulans 2-6, jeo: Jeotgalibacillus malaysiensis, bmq: Bacillus megaterium QM B1551, beo: Bacillus endophyticus, bacy: Bacillus sp. YP1, bsus: Bacillus subtilis subsp. subtilis 168, balm: Bacillus sp. LM 4-2, bjs: Bacillus sp. JS, bacl: Bacillus sp. BS34A, bae: Bacillus atrophaeus 1942, bacp: Bacillus sp. Pc3, bacb: Bacillus sp. BH072, bay: Bacillus velezensis FZB42, bao: Bacillus amyloliquefaciens DSM 7, bli: Bacillus licheniformis ATCC 14580, blh: Bacillus paralicheniformis, bgy: Bacillus glycinifermentans, bacw: Bacillus sp. WP8, bpu: Bacillus pumilus SAFR-032, gth: Parageobacillus thermoglucosidasius, gmc: Geobacillus sp. Y4.1MC1, gwc: Geobacillus sp. WCH70, gtn: Geobacillus thermodenitrificans, gsr: Geobacillus subterraneus, gjf: Geobacillus genomosp. 3, gse: Geobacillus stearothermophilus, gct: Geobacillus sp. C56-T3, gya: Geobacillus sp. Y412MC52, gyc: Geobacillus sp. Y412MC61, gte: Geobacillus thermoleovorans, gka: Geobacillus kaustophilus, ggh: Geobacillus sp. GHH01, gej: Geobacillus sp. JS12, gel: Geobacillus sp. LC300, gea: Geobacillus sp. 12AMOR1, anl: Anoxybacillus sp. B7M1, anm: Anoxybacillus sp. B2M1, aamy: Anoxybacillus amylolyticus, afl: Anoxybacillus flavithermus, agn: Anoxybacillus gonensis, bby: Bacillus bombysepticus, bce: Bacillus cereus ATCC 14579, ban: Bacillus anthracis Ames, btk: Bacillus thuringiensis 97-27, bty: Bacillus toyonensis, bwe: Bacillus weihenstephanensis KBAB4, bmyc: Bacillus mycoides 219298, bcy: Bacillus cytotoxicus, far: Fictibacillus arsenicus, fpn: Fictibacillus phosphorivorans, sat: Syntrophus aciditrophicus, len: Leptolyngbya sp. NIES-3755, glj: Gloeobacter kilaueensis, npu: Nostoc punctiforme, bco: Bacillus cellulosilyticus, bse: Bacillus selenitireducens, axl: Amphibacillus xylanus, tap: Terribacillus aidingensis, hhd: Halobacillus halophilus, vig: Virgibacillus sp. 6R, lao: Lentibacillus amyloliquefaciens, sje: Salimicrobium jeotgali, tur: Turicibacter sp. H121, say: Sulfobacillus acidophilus TPY, tmr: Thermaerobacter marianensis, lpil: Limnochorda pilosa, aac: Alicyclobacillus acidocaldarius subsp. acidocaldarius DSM 446, nth: Natranaerobius thermophilus, ctx: Ruminiclostridium thermocellum DSM 1313, clb: Clostridium sp. BNL1100.

S16 a 1 10 20 30 40 50 60 BalTS M KV P T QP I PL M M N I FR D V LP TV H R Y YD QW K E R A KS I P D PE L RA Q A L D A L E RK EFHCEGGG BsuTS M TV P E HP F GL M A K V YR D I FP LV H Q E LD IW K Q K S ES I H N SE L KA Q A T A S I R DK TFHCEGGG

70 80 90 100 110 120 BalTS I Y GL L A R D R F D E L I QF I I A Y Q I M CD Y L D N L C D QS D YL D P KD F R SL H N A L L AA L T PG EPLV BsuTS I L AL L S G S Q K Q K C V EF I I A Y Q T I SD Y L D N L C D RS T SL D P QD F R ML H A S M Q DA L T VG AELQ

130 140 150 160 170 180 BalTS N Y Y Q YR IE Q ED GG Y L H E L I ET C Q H IL V T F P S F RM V Q E N ML E L S Q LY GD L Q V H K H V V KEER BsuTS N Y Y Q FR EE Q DD SG Y L H E L V KT C Q R VL G S I E H Y DM I K P Y LL E L C G YY CD L Q V H K H V I EHER

190 200 210 220 230 240 BalTS IP R L E AW F N E H K E K MP E M TW FE F S A C TG S T L G V Y TL A TY A T K E G LT S E QA D VI K A GYFPW BsuTS VP R L E KW F T Q Y E S E LP E M EW YE F S A C AG S T L G I F CL V AY S F Q P D FT E S TA K KI R D SYFPY

250 260 270 280 290 300 BalTS VQ G VH LL L D Y FI D Q E E D I A D D EL N F L FY Y E N EE QM I ER F Q YF V QK A EE SL S T LP D P KFHR BsuTS IQ G LH IL L D Y LI D Q E E D L L E G DL N F C SY Y Q S HE EM M DR L E HF I HK A DE HL Q G IP H E NFHR

310 320 330 340 350 BalTS HI WR G I I A IY L S D EK V Q K NK E L K K K SK Q MI K M GG L PS L LF Y LN S W IY R R DK...... BsuTS LI NR G L L G VY L S D DK V A G QK E M G R L AK K LI K A SG K TS L FF Y IN G R AY R K FQKMSWMKNSK

BalTS ...... BsuTS KKAQIIC

b c d D257 D92

D253 E232 E87 D83 D88 S228 D249 D82 N224 C15-PP D85

Fig. S5. Comparison between BalTS and BsuTS. (a) Primary sequence alignment of the two proteins. This panel was prepared using ESPript.25 Distribution of the conserved residues on BalTS is shown in Movie S3. (b,c) Distribution on conserved residues on BsuTS structure shown by Cartoon (b) and Surface (c) models. The BsuTS structure was constructed by homology modelling using swiss-model server.20 Yellow and green residues are identical and similar residues as presented in panel (a). Dark gray molecule is the other molecule of the dimer. Note that no information is available regarding the oligomeric state of BsuTS. (d) Assumption of the ligand binding on BsuTS. The model is constructed as Fig. 3d with the homology modelling structure of BsuTS. Selinadiene synthase from S. pristinaespiralis bound with the ligand-analogue molecule (PDB: 4OKM, white)7 is superposed on the BsuTS structure. NSE/DTE and DDxx(D,E) motifs on selinadiene synthase, and the six characteristic aspartates of BsuTS are represented. Gray spheres represent the Mg2+ cation found between the pyrophosphate part of the ligand-analogue and selinadiene synthase.

S17 a y t i s n e t n I standard (control) TF + standard database TF + database No enzyme

K349ter

F350ter Q351ter

K352ter

M353ter

authentic 9 authentic 5

Retention time

b Name of enzymes N-terminal 258th C-terminal standard (control) Tag1 BsuTS S C367 TF + standard Trigger Factor BsuTS S C367 database Tag1 BsuTS L C367 TF + database Trigger Factor BsuTS L C367 K349ter Tag1 BsuTS S K349 F350ter Tag1 BsuTS S F350 Q351ter Tag1 BsuTS S Q351 K352ter Tag1 BsuTS S K352 M353ter Tag1 BsuTS S M353

Tag1 : the tag sequence used for the crystallographic analysis of BalTS Fig. S6. Product analyses of BsuTS variants. (a) GC-MS analyses of products. The vertical gray bars represent the retention times for the authentic 5 and 9. (b) Schematic drawing of primary structures of recombinant BsuTS proteins used for this analyses. TF is Trigger Factor tag and “TF+standard” is the recombinant used for our 19 previous work. Tag1 is composed of translation enhancing element (TEE), His6-tag and thrombin digestion site.

S18 100 x 5 69

80

81 93 60

40 67 55 95 133 20 107 120 161 272 135

0 50 100 150 200 250 300 (m/z)

Fig. S7. Mass spectrum (EI) of 6.

20 19 18 17 Ha 13 9 5 1 15 11 7 16 3 Hb 14 12 10 8 6 4 2 H H COSY HMBC

NMR data, ppm, in C6D6 NOE

NO. 1H 13C NO. 1H 13C NO. 1H 13C Ha: 5.34 (1H, d, 17.6) 113.09 (t) a 1 9 2.22 (m) 27.06 (t) 17 5.12 (2H, s) 115.97 (t) Hb: 5.10 (1H, d, 12.4) 10 5.40 (m) 124.78 (d) b 18 1.69 (3H, s) 16.10 (q) 2 6.49 (1H, dd, 17.6, 10.8) 139.42 (d) 11 134.99 (s) 19 1.72 (3H, s) 16.10 (q) 3 146.44 (s) 12 2.30 (m); 2.22 (m) 40.20 (t)c 20 1.69 (3H, s) 17.72 (q) 4 2.38 (m) 31.85 (t) a 13 2.30 (m) 27.24 (t) a 5 2.37 (m) 25.82 (t) b b 14 5.40 (m) 124.94 (d) 6 5.40 (m) 124.06 (d) 15 131.10 (s) 7 135.38 (s) c 16 1.80 (m) 25.82 (q) 8 2.30 (m); 2.22 (m) 40.13 (t) a - c The assignments may be exchangeable.

Fig. S8. NMR assignment of 6 measured in C6D.

S19 1 Fig. S9. H NMR spectrum of 6 measured in C6D6.

S20 13 Fig. S10. C NMR spectrum of 6 measured in C6D6.

S21 Fig. S11. COSY, NOESY, HSQC and HMBC spectrums of 6 measured in C6D6.

S22 Table S1. Crystallographic statistics of BalTS.

Se-Met Native Data statistics

Space group P21 P21 Cell constant a/b/c (Å) 53.08 / 151.51 / 53.81 53.35, 151.67, 53.84 β(°) 110.3 110.0 Resolution[a] 50-1.85 (1.92-1.85) 50-1.64 (1.68-1.64) # Reflections observed[a] 1,025,009 (107,023) 300,403 (19,390) # Reflections uniq[a,b] 134,161 (14,104) 92,698 (6,015) # Anomalous pairs[a] 66,437 (6,003) n/a[c] Completeness[a] 99.7% (99.7%) 94.4% (87.7%)

[a] Rmerge 6.6% (114.6%) 5.8% (67.8%) I/σ(I) [a] 21.6 (2.0) 11.3 (2.0)

[a] CC1/2 99.9 (75.5) 99.6 (69.1)

Refinement statistics

R / Rfree 0.204 / 0.229 RMS bond (Å) /angle (º) 0.0067 / 1.1187 Ramachandran 98.3% / 1.7% / 0% favored/allowed/outlier Rotamers favored/allowed/outlier 98.1% / 1.8% / 0.16% PDB ID 5YO8

[a] Values in parenthesis are those for the highest resolution shells. [b] Reflections of anomalous pairs are independently and non-independently counted for Se-Met and Native datasets, respectively. [c] not applicable

S23 Table S2 (1/3). Sequence identities between BalTS and its homologue proteins. code[a] strain #ident.[b] #res.[c] %ident.[d] dor Desulfosporosinus orientis 140 356 39.3% dmi Desulfosporosinus meridiei 138 356 38.8% dai Desulfosporosinus acidiphilus 138 356 38.8% ddh Desulfitobacterium dehalogenans 136 354 38.4% dsy Desulfitobacterium hafniense Y51 132 354 37.3% ddl Desulfitobacterium dichloroeliminans 129 354 36.4% puf Pelosinus sp. UFO1 134 355 37.7% pft Pelosinus fermentans 130 353 36.8% gfe Geosporobacter ferrireducens 127 348 36.5% toc Thermosediminibacter oceani 127 352 36.1% mas Mahella australiensis 124 387 32.0% tpz Thermacetogenium phaeum 141 361 39.1% dau Candidatus Desulforudis audaxviator 129 361 35.7% mta Moorella thermoacetica 130 354 36.7% dku Desulfotomaculum kuznetsovii 124 365 34.0% slp Syntrophothermus lipocalidus 134 352 38.1% swo Syntrophomonas wolfei 126 370 34.1% blr Brevibacillus laterosporus 147 356 41.3% bbe Brevibacillus brevis 140 351 39.9% pnp Paenibacillus naphthalenovorans 149 341 43.7% pms Paenibacillus mucilaginosus KNP414 145 343 42.3% plv Paenibacillus larvae 153 359 42.6% pow Paenibacillus sp. 32O-W 153 361 42.4% pbj Paenibacillus beijingensis 150 365 41.1% pjd Paenibacillus sp. JDR-2 149 360 41.4% pdu Paenibacillus durus 147 360 40.8% psab Paenibacillus sabinae 143 360 39.7% pste Paenibacillus stellifer 147 360 40.8% paee Paenibacillus sp. FSL R7-0331 153 360 42.5% paea Paenibacillus sp. FSL R7-0273 152 360 42.2% paeq Paenibacillus sp. FSL R5-0912 147 360 40.8% paen Paenibacillus sp. FSL P4-0081 147 360 40.8% pbd Paenibacillus borealis 148 360 41.1% paeh Paenibacillus sp. FSL H7-0357 148 360 41.1% pgm Paenibacillus graminis 147 360 40.8% pri Paenibacillus riograndensis 146 365 40.0% paej Paenibacillus sp. FSL H7-0737 148 360 41.1% paef Paenibacillus sp. FSL R5-0345 147 360 40.8% pod Paenibacillus odorifer 150 360 41.7% gym Paenibacillus sp. Y412MC10 141 360 39.2% ppeo Paenibacillus peoriae 151 359 42.1% ppy Paenibacillus polymyxa E681 151 359 42.1% pta Paenibacillus terrae 151 359 42.1% pih Paenibacillus sp. IHBB 10380 145 361 40.2% pbv Paenibacillus bovis 146 362 40.3%

S24 Table S2 (2/3). Sequence identities between BalTS and its homologue proteins. code[a] strain #ident.[b] #res.[c] %ident.[d] tco Thermobacillus composti 143 363 39.4% anx Aneurinibacillus sp. XH2 146 370 39.5% bpf Bacillus pseudofirmus 270 350 77.1% bha Bacillus halodurans 220 360 61.1% bcl Bacillus clausii 168 352 47.7% ble Bacillus lehensis 156 352 44.3% bmet Bacillus methanolicus 180 360 50.0% gst Bacillus sp. X1(2014) 169 361 46.8% baci Bacillus sp. 1NLA3E 176 379 46.4% bif Bacillus infantis 169 363 46.6% bsm Bacillus smithii 178 356 50.0% bck Bacillus coagulans 2-6 175 354 49.4% jeo Jeotgalibacillus malaysiensis 166 363 45.7% bmq Bacillus megaterium QM B1551 180 352 51.1% beo Bacillus endophyticus 176 356 49.4% bacy Bacillus sp. YP1 173 370 46.8% bsus Bacillus subtilis subsp. subtilis 168 173 370 46.8% balm Bacillus sp. LM 4-2 172 371 46.4% bjs Bacillus sp. JS 166 360 46.1% bacl Bacillus sp. BS34A 172 371 46.4% bae Bacillus atrophaeus 1942 171 359 47.6% bacp Bacillus sp. Pc3 169 359 47.1% bacb Bacillus sp. BH072 168 359 46.8% bay Bacillus velezensis FZB42 168 360 46.7% bao Bacillus amyloliquefaciens DSM 7 168 359 46.8% bli Bacillus licheniformis ATCC 14580 170 359 47.4% blh Bacillus paralicheniformis 169 359 47.1% bgy Bacillus glycinifermentans 170 359 47.4% bacw Bacillus sp. WP8 170 359 47.4% bpu Bacillus pumilus SAFR-032 170 359 47.4% gth Parageobacillus thermoglucosidasius 183 359 51.0% gmc Geobacillus sp. Y4.1MC1 183 359 51.0% gwc Geobacillus sp. WCH70 180 359 50.1% gtn Geobacillus thermodenitrificans 181 360 50.3% gsr Geobacillus subterraneus 177 360 49.2% gjf Geobacillus genomosp. 3 173 372 46.5% gse Geobacillus stearothermophilus 175 369 47.4% gct Geobacillus sp. C56-T3 175 369 47.4% gya Geobacillus sp. Y412MC52 175 369 47.4% gyc Geobacillus sp. Y412MC61 175 369 47.4% gte Geobacillus thermoleovorans 175 369 47.4% gka Geobacillus kaustophilus 175 449 39.0% ggh Geobacillus sp. GHH01 174 369 47.2% gej Geobacillus sp. JS12 175 360 48.6%

S25 Table S2 (3/3). Sequence identities between BalTS and its homologue proteins.

code[a] strain #ident.[b] #res.[c] %ident.[d] gej Geobacillus sp. JS12 175 360 48.6% gel Geobacillus sp. LC300 176 369 47.7% gea Geobacillus sp. 12AMOR1 178 360 49.4% anl Anoxybacillus sp. B7M1 171 358 47.8% anm Anoxybacillus sp. B2M1 171 358 47.8% aamy Anoxybacillus amylolyticus 176 355 49.6% afl Anoxybacillus flavithermus 175 359 48.7% agn Anoxybacillus gonensis 175 356 49.2% bby Bacillus bombysepticus 185 354 52.3% bce Bacillus cereus ATCC 14579 185 354 52.3% ban Bacillus anthracis Ames 185 354 52.3% btk Bacillus thuringiensis 97-27 184 358 51.4% bty Bacillus toyonensis 179 344 52.0% bwe Bacillus weihenstephanensis KBAB4 184 354 52.0% bmyc Bacillus mycoides 219298 183 353 51.8% bcy Bacillus cytotoxicus 186 354 52.5% far Fictibacillus arsenicus 177 356 49.7% fpn Fictibacillus phosphorivorans 169 356 47.5% sat Syntrophus aciditrophicus 175 362 48.3% len Leptolyngbya sp. NIES-3755 169 349 48.4% glj Gloeobacter kilaueensis 160 351 45.6% npu Nostoc punctiforme 175 381 45.9% bco Bacillus cellulosilyticus 190 353 53.8% bse Bacillus selenitireducens 168 352 47.7% axl Amphibacillus xylanus 150 361 41.6% tap Terribacillus aidingensis 170 360 47.2% hhd Halobacillus halophilus 165 358 46.1% vig Virgibacillus sp. 6R 153 356 43.0% lao Lentibacillus amyloliquefaciens 150 343 43.7% sje Salimicrobium jeotgali 158 342 46.2% tur Turicibacter sp. H121 127 345 36.8% say Sulfobacillus acidophilus TPY 131 349 37.5% tmr Thermaerobacter marianensis 134 496 27.0% lpil Limnochorda pilosa 111 365 30.4% Alicyclobacillus acidocaldarius subsp. aac 125 351 35.6% acidocaldarius DSM 446 nth Natranaerobius thermophilus 113 354 31.9% Ruminiclostridium thermocellum DSM ctx 85 347 24.5% 1313 clb Clostridium sp. BNL1100 80 352 22.7%

[a] Strain codes identical with Fig. S4. [b] Number of identical residues with BalTS. [c] Number of residues. [d] Identity with BalTS calculated by [b]/[c].

S26 References 1. W. Kabsch, Acta Crystallogr. D Biol. Crystallogr., 2010, 66, 125-132. 2. T. C. Terwilliger and J. Berendzen, Acta Crystallogr. D Biol. Crystallogr., 1999, 55, 849-861. 3. T. C. Terwilliger, Acta Crystallogr. D Biol. Crystallogr., 2003, 59, 38-44. 4. P. Emsley, B. Lohkamp, W. G. Scott and K. Cowtan, Acta Crystallogr. D Biol. Crystallogr., 2010, 66, 486-501. 5. A. A. Vagin, R. A. Steiner, A. A. Lebedev, L. Potterton, S. McNicholas, F. Long and G. N. Murshudov, Acta Crystallogr. D Biol. Crystallogr., 2004, 60, 2184-2195. 6. E. Krissinel and K. Henrick, J. Mol. Biol., 2007, 372, 774-797. 7. P. Baer, P. Rabe, K. Fischer, C. A. Citron, T. A. Klapschinski, M. Groll and J. S. Dickschat, Angew. Chem. Int. Ed. Engl., 2014, 53, 7652-7656. 8. M. Koksal, W. K. Chou, D. E. Cane and D. W. Christianson, Biochemistry, 2012, 51, 3011-3020. 9. L. Zhang, C. C. Chen, T. P. Ko, J. W. Huang, Y. Zheng, W. Liu, I. Wang, S. R. Malwal, X. Feng, K. Wang, C. H. Huang, S. T. Hsu, A. H. Wang, E. Oldfield and R. T. Guo, Angew. Chem. Int. Ed. Engl., 2016, 55, 4716-4720. 10. G. G. Harris, P. M. Lombardi, T. A. Pemberton, T. Matsui, T. M. Weiss, K. E. Cole, M. Koksal, F. V. t. Murphy, L. S. Vedula, W. K. Chou, D. E. Cane and D. W. Christianson, Biochemistry, 2015, 54, 7142-7155. 11. D. J. Grundy, M. Chen, V. Gonzalez, S. Leoni, D. J. Miller, D. W. Christianson and R. K. Allemann, Biochemistry, 2016, 55, 2112-2121. 12. D. A. Whittington, M. L. Wise, M. Urbansky, R. M. Coates, R. B. Croteau and D. W. Christianson, Proc. Natl. Acad. Sci. U. S. A., 2002, 99, 15375-15380. 13. K. Rudolph, C. Parthier, C. Egerer-Sieber, D. Geiger, Y. A. Muller, W. Kreis and F. Muller-Uri, Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun., 2016, 72, 16-23. 14. M. Seemann, G. Zhai, J. W. de Kraker, C. M. Paschall, D. W. Christianson and D. E. Cane, J. Am. Chem. Soc., 2002, 124, 7681-7689. 15. W. Liu, X. Feng, Y. Zheng, C. H. Huang, C. Nakano, T. Hoshino, S. Bogue, T. P. Ko, C. C. Chen, Y. Cui, J. Li, I. Wang, S. T. Hsu, E. Oldfield and R. T. Guo, Sci. Rep., 2014, 4, 6214. 16. J. M. Caruthers, I. Kang, M. J. Rynkiewicz, D. E. Cane and D. W. Christianson, J. Biol. Chem., 2000, 275, 25533-25539. 17. R. Janke, C. Gorner, M. Hirte, T. Bruck and B. Loll, Acta Crystallogr. D Biol. Crystallogr., 2014, 70, 1528-1537. 18. M. J. Rynkiewicz, D. E. Cane and D. W. Christianson, Proc. Natl. Acad. Sci. U. S. A., 2001, 98, 13543-13548. 19. T. Sato, S. Yoshida, H. Hoshino, M. Tanno, M. Nakajima and T. Hoshino, J. Am. Chem. Soc., 2011, 133, 9734-9737. 20. M. Biasini, S. Bienert, A. Waterhouse, K. Arnold, G. Studer, T. Schmidt, F. Kiefer, T. Gallo Cassarino, M. Bertoni, L. Bordoli and T. Schwede, Nucleic Acids Res., 2014, 42, W252-258. 21. T. Sato, H. Yamaga, S. Kashima, Y. Murata, T. Shinada, C. Nakano and T. Hoshino, Chembiochem, 2013, 14, 822-825. 22. D. Ueda, H. Yamaga, M. Murakami, Y. Totsuka, T. Shinada and T. Sato, Chembiochem, 2015, 16, 1371-1377. 23. L. C. Tarshis, M. Yan, C. D. Poulter and J. C. Sacchettini, Biochemistry, 1994, 33, 10871-10877. 24. C. A. Lesburg, G. Zhai, D. E. Cane and D. W. Christianson, Science, 1997, 277, 1820-1824. 25. X. Robert and P. Gouet, Nucleic Acids Res., 2014, 42, W320-324.

S27