2._CRD Calculator_NN1 development_NN1 
For_PRP bioprocesses_NN2 ,_PUN a_AT0 plant_NN1 can_VM0 be_VBI divided_VVN into_PRP upstream_AJ0 and_CJC downstream_AJ0 areas_NN2 as_CJS well_AV0 as_CJS process_NN1 utilities_NN2 ._SENT Upstream_AJ0 areas_NN2 are_VBB related_VVN to_PRP fermentation_NN1 ,_PUN while_CJS downstream_AJ0 areas_NN2 are_VBB related_VVN to_PRP product_NN1 purification_NN1 ._SENT Process_NN1 utilities_NN2 are_VBB required_VVN and_CJC can_VM0 be_VBI estimated_VVN for_PRP both_DT0 upstream_AJ0 and_CJC downstream_AJ0 areas_NN2 ._SENT Any_DT0 TEA_NN1 usually_AV0 begins_VVZ with_PRP ,_PUN and_CJC is_VBZ specific_AJ0 to_TO0 ,_PUN the_AT0 details_NN2 of_PRF the_AT0 process_NN1 being_VBG modeled_VVN ,_PUN which_DTQ historically_AV0 would_VM0 importantly_AV0 include_VVI the_AT0 target_NN1 molecule_NN1 being_VBG produced_VVN ,_PUN the_AT0 bioprocess_NN1 performance_NN1 ,_PUN and_CJC the_AT0 details_NN2 of_PRF the_AT0 downstream_AJ0 purification_NN1 ._SENT This_DT0 complexity_NN1 can_VM0 make_VVI a_AT0 generalized_AJ0 TEA_NN1 tool_NN1 difficult_AJ0 to_TO0 implement_VVI ._SENT As_CJS a_AT0 result_NN1 ,_PUN I_PNP first_ORD sought_VVD to_TO0 develop_VVI a_AT0 generalized_AJ0 ,_PUN yet_AV0 meaningful_AJ0 ,_PUN bioprocess_AJ0 model_NN1 to_TO0 enable_VVI reasonable_AJ0 cost_NN1 estimates_NN2 that_CJT are_VBB useful_AJ0 early_AV0 in_PRP the_AT0 strain_NN1 and_CJC process_NN1 development_NN1 cycle_NN1 ._SENT The_AT0 approach_NN1 taken_VVN is_VBZ illustrated_VVN in_PRP Fig._NN1 1._CRD Briefly_AV0 ,_PUN the_AT0 Bioprocess_NP0 TEA_NN1 Calculator_NN1 first_ORD accounts_VVZ for_PRP the_AT0 conversion_NN1 of_PRF glucose_NN1 to_PRP the_AT0 product_NN1 of_PRF interest_NN1 (_PUL Fig._NN1 1a_CRD )_PUR ,_PUN calculating_VVG and_CJC accounting_VVG for_PRP theoretical_AJ0 conversion_NN1 stoichiometry_NN1 ._SENT Subsequently_AV0 (_PUL Fig._NN1 1b_CRD )_PUR ,_PUN an_AT0 aerobic_AJ0 fermentation_NN1 is_VBZ modeled_VVN ,_PUN wherein_AVQ biomass_NN1 growth_NN1 is_VBZ coupled_VVN to_PRP biosynthesis_NN1 of_PRF the_AT0 target_NN1 chemical_AJ0 ,_PUN given_AJ0 user_NN1 defined_VVN performance_NN1 metrics_NN2 ._SENT This_DT0 fermentation_NN1 model_NN1 is_VBZ used_VVN for_PRP a_AT0 detailed_AJ0 estimate_NN1 of_PRF the_AT0 operating_NN1 (_PUL OPEX_NP0 )_PUR and_CJC capital_NN1 (_PUL CAPEX_NP0 )_PUR costs_NN2 of_PRF the_AT0 bioprocess_NN1 (_PUL Fig._NN1 1c_CRD )_PUR ,_PUN subject_NN1 to_PRP user_NN1 defined_VVN targets_NN2 for_PRP plant_NN1 performance_NN1 (_PUL plant_NN1 capacity_NN1 for_PRP example_NN1 )_PUR and_CJC downstream_AJ0 purification_NN1 ._SENT As_CJS downstream_AJ0 purification_NN1 (_PUL DSP_NP0 )_PUR methods_NN2 depend_VVB on_PRP the_AT0 physical_AJ0 and_CJC chemical_AJ0 properties_NN2 of_PRF the_AT0 product_NN1 ,_PUN and_CJC other_AJ0 factors_NN2 ,_PUN like_PRP purity_NN1 requirements_NN2 and_CJC the_AT0 fermentation_NN1 byproduct_NN1 profile_NN1 ,_PUN the_AT0 current_AJ0 calculator_NN1 only_AV0 performs_VVZ detailed_AJ0 estimates_NN2 for_PRP primary_AJ0 cell_NN1 removal_NN1 ,_PUN with_PRP remaining_AJ0 DSP_NP0 costs_NN2 estimated_VVN as_PRP a_AT0 percentage_NN1 of_PRF overall_AJ0 process_NN1 costs_NN2 ._SENT Effectively_AV0 ,_PUN the_AT0 bioprocess_NN1 facility_NN1 can_VM0 be_VBI thought_VVN of_PRF as_CJS being_VBG modeled_VVN as_PRP two_CRD facilities_NN2 or_CJC processes_NN2 ._SENT The_AT0 first_ORD ,_PUN a_AT0 more_AV0 detailed_AJ0 model_NN1 of_PRF a_AT0 fermentation_NN1 facility_NN1 producing_VVG clarified_AJ0 or_CJC cell_NN1 free_AJ0 fermentation_NN1 broth_NN1 ,_PUN and_CJC a_AT0 second_ORD more_AV0 crudely_AV0 modeled_VVN purification_NN1 facility_NN1 ._SENT The_AT0 DSP_NP0 is_VBZ treated_VVN as_PRP a_AT0 black_AJ0 box_NN1 producing_VVG a_AT0 purified_AJ0 chemical_AJ0 product_NN1 from_PRP the_AT0 clarified_AJ0 broth_NN1 input_NN1 ._SENT For_PRP simplicity_NN1 ,_PUN the_AT0 costs_NN2 of_PRF the_AT0 DSP_NP0 are_VBB modeled_VVN as_PRP a_AT0 user_NN1 defined_VVN fraction_NN1 of_PRF the_AT0 overall_AJ0 facility_NN1 capital_NN1 and_CJC operating_NN1 costs_NN2 ._SENT These_DT0 DSP_NP0 estimates_NN2 can_VM0 be_VBI altered_VVN by_PRP the_AT0 user_NN1 ,_PUN either_AV0 informed_VVN by_PRP a_AT0 conceptual_AJ0 DSP_NP0 process_NN1 or_CJC by_PRP more_DT0 general_AJ0 heuristics_NN2 as_CJS discussed_VVN below_AV0 ._SENT 
Lastly_AV0 ,_PUN estimates_NN2 of_PRF OPEX_NN1 and_CJC CAPEX_NN1 are_VBB used_VVN along_AVP with_PRP financial_AJ0 inputs_NN2 to_TO0 perform_VVI a_AT0 discounted_AJ0 cash_NN1 flow_NN1 analysis_NN1 (_PUL Fig._NN1 1d_NN0 )_PUR leading_AJ0 to_PRP estimated_AJ0 commercial_AJ0 outcomes_NN2 ,_PUN including_PRP the_AT0 minimum_AJ0 selling_NN1 price_NN1 needed_VVD to_TO0 achieve_VVI a_AT0 target_NN1 margin_NN1 as_CJS well_AV0 the_AT0 net_AJ0 present_AJ0 value_NN1 (_PUL NPV_NP0 )_PUR ,_PUN and_CJC internal_AJ0 rate_NN1 of_PRF return_NN1 (_PUL IRR_NP0 )_PUR for_PRP the_AT0 project_NN1 ,_PUN based_VVN on_PRP the_AT0 user_NN1 defined_VVN target_NN1 selling_VVG price_NN1 ._SENT 
2.1_CRD ._SENT Chemistry_NN1 
As_CJS illustrated_VVN in_PRP Fig._NN1 1_CRD ,_PUN the_AT0 first_ORD input_NN1 into_PRP the_AT0 calculator_NN1 is_VBZ the_AT0 target_NN1 chemical_AJ0 product_NN1 ._SENT Currently_AV0 ,_PUN the_AT0 calculator_NN1 accepts_VVZ molecules_NN2 with_PRP carbon_NN1 ,_PUN hydrogen_NN1 ,_PUN oxygen_NN1 and_CJC nitrogen_NN1 atoms_NN2 ._SENT While_CJS many_DT0 algorithms_NN2 can_VM0 be_VBI used_VVN to_TO0 balance_VVI chemical_AJ0 equations_NN2 (_PUL Herndon_NP0 ,_PUN 1997_CRD )_PUR ,_PUN I_PNP chose_VVD to_TO0 deploy_VVI a_AT0 metabolically_AV0 informed_AJ0 approach_NN1 ._SENT Firstly_AV0 ,_PUN the_AT0 problem_NN1 is_VBZ viewed_VVN from_PRP the_AT0 perspective_NN1 of_PRF the_AT0 basic_AJ0 chemical_AJ0 building_NN1 blocks_NN2 used_VVN for_PRP biosynthesis_NN1 ,_PUN namely_AV0 CO2_CRD and_CJC H2_CRD ._SENT Glucose_NN1 can_VM0 be_VBI thought_VVN of_PRF as_CJS a_AT0 combination_NN1 of_PRF these_DT0 two_CRD building_NN1 blocks_NN2 and_CJC specifically_AV0 glucose_NN1 provides_VVZ 2_CRD H2_CRD equivalents_NN2 per_PRP carbon_NN1 (_PUL CO2_CRD )_PUR ._SENT Similarly_AV0 ,_PUN any_DT0 potential_AJ0 organic_AJ0 chemical_NN1 can_VM0 be_VBI broken_VVN into_PRP carbon_NN1 (_PUL CO2_NP0 )_PUR and_CJC reducing_VVG equivalents_NN2 (_PUL H2_CRD )_PUR ._SENT Unless_CJS a_AT0 chemical_NN1 has_VHZ the_AT0 same_DT0 H2_NN1 /_PUN CO2_AJ0 balance_NN1 as_PRP glucose_NN1 (_PUL an_AT0 H2_AJ0 /_PUN CO2_AJ0 ratio_NN1 of_PRF 2_CRD )_PUR either_DT0 carbon_NN1 (_PUL CO2_NP0 )_PUR or_CJC reducing_VVG equivalents_NN2 (_PUL H2_CRD )_PUR will_VM0 be_VBI the_AT0 limiting_AJ0 reagent_NN1 and_CJC so_AV0 there_EX0 are_VBB fundamentally_AV0 three_CRD classes_NN2 of_PRF "_PUQ CHO_NN1 "_PUQ containing_VVG chemicals_NN2 when_CJS considering_VVG glucose_NN1 as_PRP a_AT0 substrate_NN1 ._SENT A_AT0 chemical_NN1 is_VBZ either_AV0 more_AV0 reduced_AJ0 than_CJS glucose_NN1 (_PUL an_AT0 H2_CRD /_PUN CO2_NP0 ratio_NN1 >_NN1 2_CRD ,_PUN for_PRP example_NN1 ethanol_NN1 or_CJC butanol_NN1 )_PUR ,_PUN neutral_AJ0 with_PRP respect_NN1 to_PRP glucose_NN1 (_PUL an_AT0 H2_CRD /_PUN CO2_NP0 ratio_NN1 =_NN1 2_CRD ,_PUN for_PRP example_NN1 lactate_NN1 )_PUR ,_PUN or_CJC more_AV0 oxidized_AJ0 than_CJS glucose_NN1 (_PUL an_AT0 H2_CRD /_PUN CO2_NP0 ratio_NN1 <_NN1 2_CRD ,_PUN for_PRP example_NN1 acetate_NN1 or_CJC malonate_NN1 )_PUR ._SENT As_CJS Equations_NN2 Equation_NN1 1_CRD ,_PUN Equation_NN1 2_CRD ,_PUN Equation_NN1 3_CRD ,_PUN Equation_NN1 4_CRD ,_PUN Equation_NN1 5_CRD ,_PUN Equation_NN1 6_CRD )_PUR illustrate_VVB ,_PUN each_DT0 of_PRF these_DT0 cases_NN2 leads_VVZ to_PRP a_AT0 different_AJ0 chemical_AJ0 equation_NN1 that_CJT needs_VVZ to_TO0 be_VBI balanced_VVN ._SENT Algorithmically_AV0 ,_PUN the_AT0 conversion_NN1 of_PRF a_AT0 given_AJ0 chemical_AJ0 input_NN1 to_PRP H2_NP0 and_CJC CO2_NP0 is_VBZ first_ORD considered_VVN ,_PUN and_CJC the_AT0 H2_AJ0 /_PUN CO2_AJ0 ratio_NN1 calculated_VVN ,_PUN after_PRP which_DTQ the_AT0 appropriate_AJ0 final_AJ0 conversion_NN1 equation_NN1 is_VBZ balanced_VVN ._SENT All_DT0 of_PRF these_DT0 equations_NN2 can_VM0 be_VBI balanced_VVN using_VVG simple_AJ0 algebra_NN1 as_CJS outlined_VVN in_PRP Supplemental_AJ0 Materials_NN2 Section_NN1 1._CRD In_PRP the_AT0 case_NN1 of_PRF chemical_AJ0 products_NN2 containing_VVG nitrogen_NN1 a_AT0 similar_AJ0 approach_NN1 is_VBZ used_VVN ,_PUN except_CJS that_CJT all_DT0 nitrogen_NN1 atoms_NN2 are_VBB assumed_VVN to_TO0 originate_VVI from_PRP ammonia_NN1 (_PUL NH3_CRD )_PUR which_DTQ also_AV0 brings_VVZ reducing_VVG equivalents_NN2 ._SENT This_DT0 is_VBZ consistent_AJ0 with_PRP basic_AJ0 biochemistry_NN1 ._SENT 
equation_NN1 Equation_NN1 1_CRD 
equation_NN1 Equation_NN1 2_CRD 
equation_NN1 Equation_NN1 3_CRD 
equation_NN1 Equation_NN1 4_CRD 
equation_NN1 Equation_NN1 5_CRD 
equation_NN1 Equation_NN1 6_CRD 
These_DT0 calculations_NN2 enable_VVB an_AT0 estimate_NN1 of_PRF the_AT0 theoretical_AJ0 yield_NN1 for_PRP the_AT0 production_NN1 of_PRF a_AT0 given_AJ0 chemical_NN1 from_PRP glucose_NN1 ._SENT This_DT0 calculation_NN1 is_VBZ based_VVN on_PRP the_AT0 potential_AJ0 theoretical_AJ0 chemical_AJ0 conversion_NN1 and_CJC does_VDZ not_XX0 assume_VVI a_AT0 particular_AJ0 biosynthetic_AJ0 pathway_NN1 or_CJC account_NN1 for_PRP thermodynamics_NN1 ._SENT Using_VVG a_AT0 particular_AJ0 biochemical_AJ0 pathway_NN1 may_VM0 result_VVI in_PRP a_AT0 theoretical_AJ0 pathway_NN1 yield_NN1 lower_AJC than_CJS the_AT0 theoretical_AJ0 chemical_AJ0 yield_NN1 ._SENT Also_AV0 ,_PUN while_CJS certain_AJ0 conversions_NN2 may_VM0 be_VBI stoichiometrically_AV0 possible_AJ0 they_PNP may_VM0 not_XX0 be_VBI energetically_AV0 feasible_AJ0 ._SENT Additionally_AV0 ,_PUN yield_VVB coefficients_NN2 for_PRP ammonia_NN1 and_CJC oxygen_NN1 ,_PUN used_VVN in_PRP calculations_NN2 in_PRP the_AT0 fermentation_NN1 model_NN1 below_AV0 ,_PUN are_VBB calculated_VVN at_PRP this_DT0 step_NN1 ._SENT These_DT0 yield_NN1 coefficients_NN2 are_VBB essentially_AV0 the_AT0 grams_NN2 of_PRF product_NN1 per_PRP gram_NN1 of_PRF ammonia_NN1 (_PUL or_CJC oxygen_NN1 )_PUR ._SENT Due_AJ0 to_PRP the_AT0 details_NN2 of_PRF the_AT0 stoichiometric_AJ0 calculations_NN2 ,_PUN the_AT0 current_AJ0 version_NN1 of_PRF the_AT0 calculator_NN1 assumes_VVZ glucose_NN1 (_PUL dextrose_NN1 )_PUR as_CJS the_AT0 carbon_NN1 and_CJC electron_NN1 source_NN1 for_PRP the_AT0 production_NN1 of_PRF any_DT0 given_AJ0 target_NN1 chemical_NN1 ._SENT Future_AJ0 improvements_NN2 may_VM0 include_VVI additional_AJ0 feedstocks_NN2 ._SENT 
2.2_CRD ._SENT Fermentation_NN1 model_NN1 
With_PRP the_AT0 theoretical_AJ0 chemistry_NN1 defined_VVN ,_PUN I_PNP developed_VVD a_AT0 basic_AJ0 model_NN1 for_PRP aerobic_AJ0 fermentation_NN1 ._SENT This_DT0 model_NN1 takes_VVZ into_PRP account_NN1 user_NN1 defined_VVN inputs_NN2 such_DT0 as_PRP the_AT0 target_NN1 titer_NN1 ,_PUN volumetric_AJ0 production_NN1 rate_NN1 and_CJC percentage_NN1 of_PRF theoretical_AJ0 yield_NN1 as_CJS illustrated_VVN in_PRP Fig._NN1 1._CRD For_PRP more_DT0 details_NN2 regarding_PRP the_AT0 fermentation_NN1 model_NN1 ,_PUN please_AV0 refer_VVB to_PRP Supplemental_AJ0 Materials_NN2 Section_NN1 2._CRD In_PRP this_DT0 model_NN1 the_AT0 percentage_NN1 of_PRF theoretical_AJ0 yield_NN1 is_VBZ based_VVN on_PRP the_AT0 theoretical_AJ0 chemical_AJ0 yield_NN1 described_VVD above_AV0 ._SENT The_AT0 user_NN1 should_VM0 account_VVI for_PRP differences_NN2 in_PRP yield_NN1 attributable_AJ0 to_PRP a_AT0 lower_AJC theoretical_AJ0 pathway_NN1 yield_NN1 for_PRP any_DT0 specific_AJ0 biochemical_AJ0 pathway_NN1 ._SENT For_PRP simplicity_NN1 ,_PUN the_AT0 calculator_NN1 assumes_VVZ growth_NN1 associated_AJ0 production_NN1 and_CJC logistic_AJ0 growth_NN1 ._SENT The_AT0 target_NN1 yield_VVB along_AVP with_PRP the_AT0 target_NN1 titer_NN1 define_VVB the_AT0 final_AJ0 amount_NN1 of_PRF product_NN1 and_CJC dictate_VVB the_AT0 available_AJ0 sugar_NN1 (_PUL not_XX0 used_VVN for_PRP product_NN1 synthesis_NN1 )_PUR which_DTQ can_VM0 be_VBI used_VVN for_PRP biomass_NN1 growth_NN1 ,_PUN as_CJS described_VVN in_PRP Fig._NN1 2._CRD Biomass_NN1 is_VBZ modeled_VVN as_PRP a_AT0 byproduct_NN1 chemical_NN1 (_PUL C3.85H6.69O1.78N_NP0 )_PUR with_PRP a_AT0 molecular_AJ0 weight_NN1 of_PRF 95.37_CRD g_NN0 /_PUN mol_NN1 ,_PUN which_DTQ is_VBZ produced_VVN from_PRP glucose_NN1 at_PRP 80_CRD %_NN0 of_PRF theoretical_AJ0 yield_NN1 ._SENT (_PUL Battley_NP0 ,_PUN 1987_CRD ;_PUN Grosz_NP0 and_CJC Stephanopoulos_NP0 ,_PUN 1983_CRD )_PUR ._SENT As_CJS a_AT0 result_NN1 the_AT0 user_NN1 input_NN1 titer_NN1 and_CJC percent_NN0 of_PRF theoretical_AJ0 yield_NN1 are_VBB used_VVN to_TO0 estimate_VVI the_AT0 final_AJ0 biomass_NN1 levels_NN2 at_PRP the_AT0 end_NN1 of_PRF fermentation_NN1 ._SENT 
The_AT0 total_AJ0 fermentation_NN1 time_NN1 is_VBZ calculated_VVN from_PRP the_AT0 titer_NN1 and_CJC average_AJ0 volumetric_AJ0 production_NN1 rate_NN1 ._SENT The_AT0 starting_NN1 biomass_NN1 level_NN1 is_VBZ assumed_VVN to_TO0 be_VBI 1_CRD %_NN0 of_PRF the_AT0 final_AJ0 biomass_NN1 (_PUL based_VVN on_PRP a_AT0 1_CRD %_NN0 inoculum_NN1 of_PRF a_AT0 similarly_AV0 dense_AJ0 seed_NN1 culture_NN1 )_PUR ._SENT As_CJS mentioned_VVN a_AT0 logistic_AJ0 growth_NN1 rate_NN1 is_VBZ assumed_VVN and_CJC calculated_VVN based_VVN on_PRP final_AJ0 and_CJC initial_AJ0 biomass_NN1 levels_NN2 and_CJC the_AT0 fermentation_NN1 time_NN1 ._SENT Finally_AV0 the_AT0 product_NN1 to_PRP cell_NN1 ratio_NN1 ,_PUN a_AT0 measure_NN1 of_PRF growth_NN1 associated_VVN product_NN1 biosynthesis_NN1 ,_PUN is_VBZ calculated_VVN ._SENT This_DT0 ratio_NN1 is_VBZ in_PRP effect_NN1 the_AT0 gram_NN1 of_PRF product_NN1 made_VVN per_PRP gram_NN1 of_PRF biomass_NN1 as_PRP the_AT0 cells_NN2 grow_VVB ._SENT This_DT0 can_VM0 be_VBI used_VVN to_TO0 estimate_VVI a_AT0 logistic_AJ0 product_NN1 formation_NN1 rate_NN1 ._SENT 
Together_AV0 the_AT0 above_AJ0 calculations_NN2 lead_VVB to_PRP a_AT0 fermentation_NN1 time_NN1 course_NN1 ,_PUN which_DTQ can_VM0 be_VBI used_VVN for_PRP basic_AJ0 material_NN1 and_CJC energy_NN1 balances_NN2 and_CJC to_TO0 estimate_VVI process_NN1 requirements_NN2 including_PRP raw_AJ0 materials_NN2 ,_PUN oxygen_NN1 demand_NN1 and_CJC oxygen_NN1 transfer_NN1 rates_NN2 and_CJC cooling_AJ0 requirements_NN2 ,_PUN which_DTQ in_PRP turn_NN1 can_VM0 be_VBI used_VVN with_PRP other_AJ0 inputs_NN2 to_TO0 estimate_VVI operating_NN1 and_CJC capital_NN1 costs_NN2 ._SENT 
2.3_CRD ._SENT Downstream_AJ0 purification_NN1 
Currently_AV0 ,_PUN the_AT0 calculator_NN1 specifically_AV0 estimates_VVZ the_AT0 costs_NN2 associated_VVN with_PRP primary_AJ0 cell_NN1 removal_NN1 ,_PUN which_DTQ is_VBZ modeled_VVN as_PRP centrifugation_NN1 ._SENT These_DT0 costs_NN2 are_VBB standard_AJ0 in_PRP most_DT0 bioprocesses_NN2 ,_PUN whether_CJS the_AT0 product_NN1 is_VBZ in_PRP the_AT0 supernatant_NN1 or_CJC the_AT0 cell_NN1 pellet_NN1 ._SENT However_AV0 ,_PUN the_AT0 calculator_NN1 currently_AV0 only_AV0 enables_VVZ the_AT0 user_NN1 to_TO0 estimate_VVI additional_AJ0 downstream_AJ0 purification_NN1 operating_NN1 and_CJC capital_NN1 costs_NN2 as_PRP a_AT0 fraction_NN1 of_PRF total_AJ0 costs_NN2 without_PRP any_DT0 detailed_AJ0 estimates_NN2 of_PRF these_DT0 unit_NN1 operations_NN2 ._SENT Importantly_AV0 ,_PUN the_AT0 current_AJ0 estimates_NN2 assume_VVB a_AT0 single_AJ0 byproduct_NN1 :_PUN carbon_NN1 dioxide_NN1 ._SENT All_DT0 dextrose_NN1 not_XX0 going_VVG to_TO0 produce_VVI biomass_NN1 or_CJC product_NN1 is_VBZ completely_AV0 oxidized_VVN to_PRP carbon_NN1 dioxide_NN1 ._SENT In_PRP most_DT0 cases_NN2 this_DT0 likely_AJ0 overestimates_NN2 the_AT0 oxygen_NN1 requirements_NN2 of_PRF the_AT0 process_NN1 and_CJC represents_VVZ a_AT0 worse_AJC case_NN1 scenario_NN1 with_PRP respect_NN1 to_PRP aeration_NN1 ,_PUN however_AV0 this_DT0 also_AV0 represents_VVZ a_AT0 best_AJS case_NN1 scenario_NN1 with_PRP respect_NN1 to_PRP DSP_NP0 ._SENT Real_AJ0 world_NN1 downstream_AJ0 purification_NN1 processes_NN2 must_VM0 often_AV0 deal_VVI with_PRP the_AT0 removal_NN1 of_PRF several_DT0 unwanted_AJ0 organic_AJ0 byproducts_NN2 ,_PUN which_DTQ are_VBB a_AT0 function_NN1 of_PRF the_AT0 product_NN1 and_CJC biosynthetic_AJ0 pathway_NN1 ,_PUN as_CJS well_AV0 as_CJS strain_NN1 and_CJC process_NN1 conditions_NN2 deployed_VVN ._SENT 
Capital_NN1 costs_NN2 associated_VVN with_PRP DSP_NP0 can_VM0 range_VVI widely_AV0 depending_VVG on_PRP the_AT0 complexity_NN1 of_PRF the_AT0 DSP_NP0 and_CJC number_NN1 of_PRF unit_NN1 operations_NN2 required_VVN ._SENT Simple_AJ0 distillation_NN1 ,_PUN such_DT0 as_CJS is_VBZ used_VVN for_PRP ethanol_NN1 ,_PUN may_VM0 be_VBI on_PRP the_AT0 lower_AJC end_NN1 (_PUL ~_NN1 20_CRD %_NN0 )_PUR ,_PUN whereas_CJS DSPs_NP0 requiring_VVG chromatographic_AJ0 separations_NN2 or_CJC electrodialysis_NN1 would_VM0 be_VBI anticipated_VVN to_TO0 account_VVI for_PRP 50_CRD –_PUN 70_CRD %_NN0 of_PRF total_AJ0 capital_NN1 costs_NN2 (_PUL Gunukula_NP0 and_CJC Anex_NP0 ,_PUN 2017_CRD ;_PUN Bechthold_NP0 et_NP0 al._NP0 ,_PUN 2008_CRD ;_PUN Cheng_NP0 et_NP0 al._NP0 ,_PUN 2012_CRD ;_PUN Xiu_NP0 and_CJC Zeng_NP0 ,_PUN 2008_CRD )_PUR ._SENT Operating_NN1 costs_NN2 for_PRP DSP_NP0 are_VBB often_AV0 a_AT0 smaller_AJC fraction_NN1 of_PRF the_AT0 total_AJ0 percentage_NN1 of_PRF OPEX_NN1 ,_PUN and_CJC I_PNP recommend_VVB from_PRP 20_CRD %_NN0 at_PRP the_AT0 low_AJ0 end_NN1 to_PRP 50_CRD %_NN0 at_PRP the_AT0 high_AJ0 end_NN1 (_PUL Straathof_NP0 ,_PUN 2011_CRD )_PUR ._SENT Fig._NN1 3_CRD ,_PUN adapted_VVN from_PRP data_NN0 presented_VVN by_PRP Straathof_NP0 (_PUL 2011_CRD )_PUR relates_VVZ the_AT0 reported_AJ0 percent_NN0 of_PRF production_NN1 costs_NN2 attributed_VVN to_PRP downstream_AJ0 purification_NN1 for_PRP a_AT0 variety_NN1 of_PRF molecules_NN2 ._SENT These_DT0 data_NN0 can_VM0 be_VBI used_VVN for_PRP rough_AJ0 estimates_NN2 of_PRF DSP_NP0 costs_NN2 for_PRP different_AJ0 types_NN2 of_PRF products_NN2 ._SENT Additionally_AV0 it_PNP is_VBZ worth_PRP noting_VVG that_CJT if_CJS the_AT0 fermentation_NN1 process_NN1 producing_VVG clarified_AJ0 broth_NN1 is_VBZ not_XX0 financially_AV0 attractive_AJ0 with_PRP a_AT0 low_AJ0 cost_NN1 DSP_NP0 ,_PUN the_AT0 DSP_NP0 details_NN2 are_VBB likely_AJ0 not_XX0 a_AT0 critical_AJ0 priority_NN1 until_PRP the_AT0 fermentation_NN1 process_NN1 itself_PNX has_VHZ been_VBN further_AV0 optimized_VVN ._SENT When_CJS DSP_NP0 details_NN2 are_VBB critical_AJ0 for_PRP a_AT0 project_NN1 to_PRP advance_NN1 ,_PUN additional_AJ0 models_NN2 ,_PUN beyond_PRP this_DT0 calculator_NN1 ,_PUN would_VM0 need_VVI to_TO0 be_VBI built_VVN ._SENT 
2.4_CRD ._SENT Operating_NN1 and_CJC capital_NN1 cost_NN1 estimates_NN2 
The_AT0 current_AJ0 version_NN1 of_PRF the_AT0 Bioprocess_NP0 TEA_NN1 Calculator_NN1 assumes_VVZ the_AT0 construction_NN1 of_PRF a_AT0 new_AJ0 facility_NN1 in_PRP a_AT0 Build-Own-Operate_NN1 (_PUL BOO_NN1 )_PUR Financial_AJ0 model_NN1 ._SENT Estimated_AJ0 operating_NN1 and_CJC capital_NN1 costs_NN2 assume_VVB a_AT0 general_AJ0 plant_NN1 configuration_NN1 as_CJS illustrated_VVN in_PRP Fig._NN1 4._CRD Briefly_AV0 the_AT0 facility_NN1 can_VM0 be_VBI broken_VVN down_AVP into_PRP the_AT0 following_AJ0 6_CRD key_AJ0 areas_NN2 including_PRP 1_CRD )_PUR Main_AJ0 fermentation_NN1 2_CRD )_PUR Seed_NN1 fermentation_NN1 ,_PUN 3_CRD )_PUR Primary_AJ0 cell_NN1 removal_NN1 ,_PUN 4_CRD )_PUR Process_NN1 utilities_NN2 ,_PUN 5_CRD )_PUR Downstream_AJ0 purification_NN1 ,_PUN and_CJC 6_CRD )_PUR associated_AJ0 infrastructure_NN1 (_PUL warehousing_NN1 and_CJC office_NN1 buildings_NN2 ,_PUN site_NN1 development_NN1 etc_AV0 )_PUR ._SENT In_PRP this_DT0 brownfield_AJ0 design_NN1 utilities_NN2 for_PRP the_AT0 process_NN1 are_VBB modeled_VVN but_CJC main_AJ0 gas_NN1 lines_NN2 and_CJC electrical_AJ0 supply_NN1 are_VBB provided_VVN to_PRP the_AT0 facility_NN1 ._SENT Additionally_AV0 ,_PUN while_CJS waste_NN1 is_VBZ initially_AV0 heated_AJ0 and_CJC pH_NN1 adjusted_VVN ,_PUN a_AT0 wastewater_AJC treatment_NN1 plant_NN1 is_VBZ not_XX0 considered_VVN in_PRP this_DT0 design_NN1 ,_PUN and_CJC would_VM0 need_VVI to_TO0 be_VBI provided_VVN via_PRP colocation_NN1 ._SENT The_AT0 heating_NN1 of_PRF the_AT0 waste_NN1 biomass_NN1 (_PUL at_PRP 60_CRD °_NN0 C_ZZ0 )_PUR is_VBZ to_TO0 kill_VVI any_DT0 surviving_AJ0 bacterial_AJ0 cells_NN2 prior_AJ0 to_TO0 transfer_VVI to_PRP a_AT0 wastewater_AJC treatment_NN1 facility_NN1 ._SENT This_DT0 is_VBZ a_AT0 conservative_AJ0 step_NN1 that_CJT may_VM0 not_XX0 be_VBI needed_VVN for_PRP many_DT0 microbial_AJ0 processes_NN2 ._SENT 
Operating_NN1 costs_NN2 are_VBB estimated_VVN prior_AJ0 to_PRP capital_NN1 costs_NN2 ,_PUN as_CJS many_DT0 of_PRF the_AT0 capital_NN1 estimates_NN2 depend_VVB on_PRP the_AT0 OPEX_NN1 ._SENT Operating_NN1 costs_NN2 estimates_NN2 include_VVB variable_AJ0 costs_NN2 such_DT0 as_PRP raw_AJ0 materials_NN2 and_CJC utilities_NN2 as_CJS well_AV0 as_CJS fixed_AJ0 operating_NN1 costs_NN2 including_PRP labor_NN1 and_CJC additional_AJ0 fixed_AJ0 costs_NN2 ._SENT For_PRP more_DT0 details_NN2 on_PRP specific_AJ0 calculations_NN2 underlying_AJ0 estimates_NN2 refer_VVB to_PRP Supplemental_AJ0 Materials_NN2 Sections_NN2 3_CRD Use_VVB cases_NN2 and_CJC limitations_NN2 ,_PUN 4_CRD A_AT0 technoeconomic_AJ0 analysis_NN1 of_PRF an_AT0 aerobic_AJ0 bioprocess_NN1 for_PRP diethyl_NN1 malonate_NN1 production_NN1 ._SENT The_AT0 calculator_NN1 estimates_VVZ the_AT0 raw_AJ0 materials_NN2 and_CJC process_NN1 utilities_NN2 needed_VVD given_VVN the_AT0 target_NN1 plant_NN1 capacity_NN1 and_CJC fermentation_NN1 performance_NN1 as_CJS well_AV0 as_CJS other_AJ0 user_NN1 defined_VVN inputs_NN2 ._SENT Raw_AJ0 materials_NN2 and_CJC utilities_NN2 estimated_VVN include_VVB :_PUN water_NN1 ,_PUN glucose_NN1 ,_PUN ammonia_NN1 ,_PUN and_CJC the_AT0 costs_NN2 of_PRF CIP_NN1 (_PUL clean_AJ0 in_PRP place_NN1 )_PUR reagents_NN2 ,_PUN electricity_NN1 ,_PUN steam_NN1 and_CJC compressed_AJ0 air_NN1 ._SENT Glucose_NN1 costs_NN2 are_VBB estimated_VVN based_VVN on_PRP the_AT0 user_NN1 defined_VVN glucose_NN1 price_NN1 as_CJS well_AV0 as_CJS the_AT0 overall_AJ0 fermentation_NN1 yield_NN1 and_CJC yield_NN1 in_PRP the_AT0 DSP_NP0 ._SENT First_ORD the_AT0 amount_NN1 of_PRF glucose_NN1 needed_VVN for_PRP product_NN1 biosynthesis_NN1 and_CJC biomass_NN1 production_NN1 are_VBB calculated_VVN as_CJS described_VVN above_AV0 to_TO0 give_VVI a_AT0 target_NN1 fermentation_NN1 yield_NN1 ._SENT The_AT0 fermentation_NN1 yield_NN1 together_AV0 with_PRP the_AT0 overall_AJ0 DSP_NP0 yield_NN1 (_PUL as_CJS input_VVN by_PRP the_AT0 user_NN1 )_PUR defines_VVZ the_AT0 total_AJ0 glucose_NN1 needed_VVN ._SENT The_AT0 default_NN1 glucose_NN1 pricing_NN1 is_VBZ at_PRP $_NN0 0.18_CRD /_PUN lb_NN0 which_DTQ corresponds_VVZ to_PRP bulk_NN1 2020_CRD pricing_NN1 for_PRP DE95_CRD corn_NN1 syrup_NN1 ,_PUN which_DTQ is_VBZ usually_AV0 >_NN1 650_CRD g_ZZ0 /_PUN L_ZZ0 dextrose_NN1 ._SENT Lower_AJC "_PUQ over_PRP the_AT0 fence_NN1 "_PUQ prices_NN2 may_VM0 be_VBI achievable_AJ0 when_CJS co-locating_VVG a_AT0 facility_NN1 with_PRP a_AT0 sugar_NN1 mill_NN1 ._SENT Ammonia_NN1 costs_NN2 are_VBB estimated_VVN similarly_AV0 to_PRP glucose_NN1 costs_NN2 ._SENT 
