Claims:We Claim:

1. A method for selecting one or more pathways, by combining one or more chemical and one or more biochemical processes, for one of a synthesis and degradation of a target molecule, comprising:

receiving input of one or more pathways for one of the synthesis and degradation of the of one or more target molecules,
wherein the one or more pathways comprise sequential arrangement of the one or more reaction steps, and
wherein the one or more reaction steps forming the one or more pathways being one of a chemical reaction step performed by chemical process and biochemical reaction step performed by biochemical process;

determining number of the one or more pathways received;

predicting a plurality of permutations in hybrid arrangements of the one or more reaction steps of the received pathway, if the determined number of the one or more pathways received as the input equals to one,
wherein each of the one more reaction steps being one of a biochemical process and chemical process;

computing reaction feasibility score for each of the reaction steps of the plurality of hybrid arrangements predicted for the received pathway with reference to a knowledgebase,
wherein the reaction feasibility score is computed based on at least one of parameters of yield of step, distance of the reaction step from a reference reaction step available in the knowledgebase, and catalyst availability, and
wherein the parameter of the catalyst availability for the biochemical reaction step refers to availability of one or more enzymes related to the biochemical reaction step, and the catalyst availability for the chemical reaction step refers to availability of one or more catalysts related to the chemical reaction step;

computing pathway feasibility score for all the plurality of the hybrid arrangements predicted for the received pathway based on the computed reaction feasibility score for each of the one or more reaction steps of the plurality of the hybrid arrangements predicted for the received pathway;

sorting the plurality of the hybrid arrangements predicted for the received pathway based on the computed pathway feasibility score; and

selecting the one or more hybrid arrangements predicted for the received pathway for one of the synthesis and degradation of the target molecule based on the computed pathway feasibility score.

2. The method as claimed in claim 1, wherein the knowledgebase comprises one or more biochemical reactions, one or more chemical reactions, information regarding at least one of thermodynamic feasibility and kinetic feasibility of the one or more biochemical reactions and one or more chemical reactions, information regarding at least one of catalyst information and yield for each of the one or more biochemical reactions and one or more chemical reactions.

3. The method as claimed in claim 1, wherein the availability of one or more enzymes related to the biochemical reaction step is assessed based on phylogenetic distance between an organism where biochemical reaction being carried out to one or more reference organisms having similar or same one or more enzymes.

4. The method as claimed in claim 1, wherein the availability of one or more catalysts related to the chemical reaction step is assessed based on distance between the one or more catalysts to most similar one or more catalysts.

5. The method as claimed in claim 1, wherein the reaction feasibility score is computed by a mathematical function combining independent scores of the parameters of yield of step, distance of the reaction step from a reference reaction step available in the knowledgebase, and catalyst availability associated with an individual reaction step.

6. The method as claimed in claim 1, wherein pathway feasibility score is computed by a mathematical function combining the reaction feasibility score for each of the one or more reaction steps forming the predicted hybrid arrangements of the received pathway.

7. The method as claimed in claim 1, wherein the one or more hybrid arrangements of the received pathway are selected when the pathway feasibility score is greater or equal to a preset threshold score.

8. The method as claimed in claim 1, further comprising imposing a penalty by way of reducing the pathway feasibility score of the individual hybrid arrangement of the received pathway by a predetermined number.

9. The method as claimed in claim 8, wherein the penalty is imposed for every approach transition from the one type of process to another type of process in the sequential arrangement of the reaction steps.

10. The method as claimed in claim 8, wherein the penalty is imposed after exempting first approach transition from the one type of process to another type of process in the sequential arrangement of the reaction steps.

11. The method as claimed in claim 8, wherein the penalty imposed incrementally increases from lower to higher predetermined number as number of the approach transitions from the one type of process to another type of process increase in the sequential arrangement of the reaction steps.

12. The method as claimed in claim 1, further comprising:
ranking the selected one or more hybrid arrangements of the one or more received pathways based on a preset criteria; and
selecting one or more of the top ranked hybrid arrangements of the one or more received pathways.

13. The method as claimed in claim 1, further comprising:
if the determined number of the one or more pathways received as the input is more than one, performing at least one of –
(a) predicting a plurality of permutations in hybrid arrangement of the one or more reaction steps of the received input pathways, and
(b) computing the pathway feasibility score for each of the input pathways;
sorting the input pathways based on the pathway feasibility score; and
selecting the sorted input pathways.

14. The method as claimed in claim 13, further comprising predicting a plurality of permutations in hybrid arrangement of the one or more reaction steps of the sorted input pathways.

15. The method as claimed in claim 1, further comprising:
processing the input of the one or more pathways to identify at least one of a biochemical and chemical nature of the one or more pathways, similarity in the reaction steps of the one or more pathways, and similarity of the one or more target molecules on which the one or more pathways are working on, if the determined number of the one or more pathways received as the input is more than one;
computing the pathway feasibility score for the input pathways, when it is identified that all of the input pathways are either biochemical or chemical having different reaction steps but producing the similar target molecule.;

16. The method as claimed in claim 1, further comprising:
processing the input of the one or more pathways to identify at least one of a biochemical and chemical nature of the one or more pathways, similarity in the reaction steps of the one or more pathways, and similarity of the one or more target molecules on which the one or more pathways are working on, if the determined number of the one or more pathways received as the input is more than one; and
computing the pathway feasibility score for the input pathways, when it is identified that the input pathways are mixture of biochemical and chemical, having different reaction steps but producing the similar target molecule.

17. A device for selecting one or more pathways, by combining one or more chemical and one or more biochemical processes, for one of a synthesis and degradation of a target molecule, comprising:
a memory; and
one or more processors operatively coupled to the memory, the one or more processors are configured to perform the steps of:

receiving input of one or more pathways for one of the synthesis and degradation of the of one or more target molecules,
wherein the one or more pathways comprise sequential arrangement of the one or more reaction steps, and
wherein the one or more reaction steps forming the one or more pathways being one of a chemical reaction step performed by chemical process and biochemical reaction step performed by biochemical process;

determining number of the one or more pathways received;

predicting a plurality of permutations in hybrid arrangement of the one or more reaction steps of the received pathway, if the determined number of the one or more pathways received as the input equals to one,
wherein each of the one more reaction step being one of a biochemical process and chemical process;

computing reaction feasibility score for each of the reaction steps of the plurality of hybrid arrangement predicted for the received pathway with reference to a knowledgebase,
wherein the reaction feasibility score is computed based on at least one of parameters of yield of step, distance of the reaction step from a reference reaction step available in the knowledgebase, and catalyst availability, and
wherein the parameter of the catalyst availability for the biochemical reaction step refers to availability of one or more enzymes related to the biochemical reaction step, and the catalyst availability for the chemical reaction step refers to availability of one or more catalysts related to the chemical reaction step;

computing pathway feasibility score for all the plurality of the hybrid arrangements predicted for the received pathway based on the computed reaction feasibility score for each of the one or more reaction steps;

sorting the plurality of the hybrid arrangements predicted for the received pathway based on the computed pathway feasibility score; and

selecting the one or more hybrid arrangements predicted for the received pathway for one of the synthesis and degradation of the target molecule based on the computed pathway feasibility score.

18. The device as claimed in claim 17, wherein the one or more processors are further configured to perform the step of: imposing a penalty by way of reducing the pathway feasibility score of the individual hybrid arrangement of the received pathway by a predetermined number.

19. The device as claimed in claim 17, wherein the one or more processors are further configured to perform the at least one of steps, if the determined number of the one or more pathways received as the input is more than one:
(a) predicting a plurality of permutations in hybrid arrangement of the one or more reaction steps of the received input pathways, and
(b) computing the pathway feasibility score for each of the input pathways;
sorting the input pathways based on the pathway feasibility score; and
selecting the sorted input pathways.

Dated this the 13th day of February 2016
Signature

KEERTHI JS
Patent Agent
Agent for the Applicant

, Description:FORM 2

THE PATENTS ACT, 1970
(39 OF 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(Section 10 and Rule 13)

METHOD FOR SELECTING PATHWAY(S), BY COMBINING CHEMICAL AND BIOCHEMICAL PROCESS(ES), FOR SYNTHESIS OR DEGRADATION OF A TARGET MOLECULE

SAMSUNG R&D INSTITUTE INDIA – BANGALORE PRIVATE LIMITED
# 2870, ORION Building, Bagmane Constellation Business Park,
Outer Ring Road, Doddanakundi Circle,
Marathahalli Post, Bangalore-560 037

An Indian Company

The following Specification particularly describes the invention and the manner in which it is to be performed
FIELD OF THE INVENTION
The present invention relates to selecting chemical and biochemical synthesis/degradation strategies for transforming target compound of interest, and more particularly it relates to method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule.

BACKGROUND OF THE INVENTION

Target molecules are either synthesized or degraded through chemical transformations and the processing is the heart of chemical industry. The processing requires chemical transformations of the target compound through either a chemical or biochemical approach. These approaches have their advantages and limitations. Processing based on a chemical approach is easy to scale up and typically reports a higher kinetic rate. They are amiable to greater process conditions. However, chemical approaches often report poor efficiency for complex molecular and multiple step reactions. Given the number of cross reactions, specificity in chemical transformations is often a challenge. Alternatively, a biochemical based process reports higher synthetic specificity and can perform multiple chemical conversions within a singular cell with no requirement of intermediate purification step(s). An additional advantage of the biochemical process is that it is often performed under a milder condition. However, it must be noted that biochemical based transformations are not as exhaustive as chemical. Moreover, optimization of strain or micro-organism which hosts biochemical transformations is not trivial.
It may thus be noted that neither biochemical nor chemical processes provide an efficient and effective strategy for constructing a pathway for transforming a target molecule.

An optimized process design would thus consider a hybrid approach (combination of both chemical and biochemical strategies) against a single approach based on chemical or biochemical. However, designing of an optimized hybrid approach for processing chemicals is challenging and its experimental design is often not feasible.

In view of the foregoing, there is a need for a method and/or device to enable a user to select effective chemical and biochemical synthesis/ degradation strategies for transforming a target compound of interest through a hybrid approach.

The above mentioned shortcomings and problems are addressed through the below specifications.

SUMMARY OF THE INVENTION

The various embodiments of the present invention disclose method and device for selecting pathway(s), by combining chemical and biochemical process(es), for one of a synthesis and degradation of a target molecule.

In an embodiment of the present invention, a method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule is disclosed. The first step of the method is receiving input of pathway(s) for synthesis or degradation of the target molecule(s). The pathway(s) so received comprise sequential arrangement of the reaction step(s), and the reaction step(s) forming the pathway(s) are either chemical reaction step(s) performed by chemical process or biochemical reaction step(s) performed by biochemical process. Next step includes determining number of the pathway(s) received. In further step, if the determined number of the pathway(s) received as the input equals to one, then predicting a plurality of permutations in hybrid arrangements of the reaction step(s) of the received pathway, wherein each of the reaction steps is either the biochemical process or a chemical process. Further to that, computing reaction feasibility score for each of the reaction steps of the plurality of hybrid arrangements predicted for the received pathway with reference to a knowledgebase. The reaction feasibility score is computed based on parameters of yield of step and/or distance of the reaction step from a reference reaction step available in the knowledgebase and/or catalyst availability. The parameter of the catalyst availability for the biochemical reaction step refers to availability of enzyme(s) related to the biochemical reaction step, and for the chemical reaction step it refers to availability of catalyst(s) related to the chemical reaction step. Next step is computing pathway feasibility score for all the plurality of the hybrid arrangements predicted for the received pathway based on the computed reaction feasibility score for each of the reaction step(s) of the plurality of the hybrid arrangements predicted for the received pathway. Further to that, sorting the plurality of the hybrid arrangements predicted for the received pathway based on the computed pathway feasibility score. Finally, selecting hybrid arrangement(s) of the received pathway for the synthesis or degradation of the target molecule based on the computed pathway feasibility score.

In another embodiment of the method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule further includes step of imposing a penalty by way of reducing the pathway feasibility score of each of the individual hybrid arrangements of the received pathway by a predetermined number.

In another embodiment of the method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule further includes steps of ranking the selected hybrid arrangement(s) of the received pathway(s) based on preset criteria and selecting one or more of the top ranked hybrid arrangements of the received pathway.

In yet another embodiment of the method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule further includes performing one of following steps, where the determined number of the one or more pathways received as the input is more than one: (a) predicting a plurality of permutations in hybrid arrangements of the reaction step(s) of the received input pathways, and (b) computing the pathway feasibility score for each of the input pathways; sorting the input pathways based on the pathway feasibility score; and selecting the sorted input pathways. Further to this, predicting a plurality of permutations in hybrid arrangements of the reaction step(s) for the selected pathways.

In yet another embodiment of the method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule further includes following steps if the determined number of the pathway(s) received as the input is more than one: processing the input of the pathways to identify biochemical and chemical nature of the pathway(s) or/and similarity in the reaction steps of the pathway(s) or/and similarity of the target molecule(s) on which the pathway(s) are working on; computing the pathway feasibility score for the input pathways, when it is identified that all of the input pathways are either biochemical or chemical, having different reaction steps but producing the similar target molecule; sorting the input pathways based on the computed pathway feasibility score; and selecting the sorted input pathway(s) based on the pathway feasibility score.

In yet another embodiment of the method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule further includes following steps if the determined number of the pathway(s) received as the input is more than one: processing the input of the pathway(s) to identify biochemical and chemical nature of the pathway(s) and/or similarity in the reaction steps of the pathway(s) and/or and similarity of the target molecule(s) on which the pathway(s) are working on; computing the pathway feasibility score for the input pathways, when it is identified that the input pathways are mixture of biochemical and chemical, having different reaction steps but producing the similar target molecule; sorting the input pathways based on the computed pathway feasibility score; selecting the pathways from the identified input pathways based on the pathway feasibility score; and predicting a plurality of permutations in hybrid arrangements of the reaction steps of the selected pathway(s).

In an embodiment of the present invention, a device for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule is disclosed. The device includes a memory; and processor(s) operatively coupled to the memory. The processor(s) is/are configured to perform the steps including: receiving input of pathway(s) for synthesis or degradation of the target molecule(s); determining number of the pathway(s) received; predicting a plurality of permutations in hybrid arrangements of the reaction step(s) of the received pathway, if the determined number of the pathway(s) received as the input equals to one; computing reaction feasibility score for each of the reaction steps of the plurality of hybrid arrangement predicted for the received pathway with reference to a knowledgebase; computing pathway feasibility score for all the plurality of the hybrid arrangements predicted for the received pathway based on the computed reaction feasibility score for each of the reaction step(s); sorting the plurality of the hybrid arrangements predicted for the received pathway based on the computed pathway feasibility score; and selecting the hybrid arrangement(s) predicted for the received pathway for one of the synthesis and degradation of the target molecule based on the computed pathway feasibility score.

In another embodiment of the device for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule, the processor(s) is/are further configured to perform the step of imposing a penalty by way of reducing the pathway feasibility score of the individual hybrid arrangement of the received pathway by a predetermined number.

In yet another embodiment of the device for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule, the processor(s) is/are further configured to perform the steps if the determined number of the pathways received as the input is more than one: (a) predicting a plurality of permutations in hybrid arrangement of the reaction steps of the received input pathways; or (b) computing the pathway feasibility score for each of the input pathways, sorting the input pathways based on the pathway feasibility score, and selecting the sorted input pathways.

These and other aspects of the embodiments herein will be better appreciated and understood when considered in conjunction with the following description and the accompanying drawings. It should be understood, however, that the following descriptions, while indicating preferred embodiments and numerous specific details thereof, are given by way of illustration and not of limitation. Many changes and modifications may be made within the scope of the embodiments herein without departing from the spirit thereof, and the embodiments herein include all such modifications.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS
The other objects, features and advantages will occur to those skilled in the art from the following description of the preferred embodiment and the accompanying drawings in which:

Figure 1 is schematic of chemical process of compound A to compound B, where the processing can be performed, chemically, biochemically or by a combination of both.
Figure 2 is a schematic flow representation of a method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule, according to an embodiment.

Figure 4 illustrates an exemplary embodiment of chemical and biochemical based 3 step synthesis of Adipic acid from 3, 4-Dihydroxybenzonate.

Figure 5 illustrates an exemplary embodiment of 3 step synthesis of the industrially important chemical 1,3 butadiene from 5-Hydroxy-3-oxopentanoate.

Figure 6 is a schematic flow representation of a method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule, according to another embodiment.

Figure 7 is a block level diagram of a device for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule, according to another embodiment.

Although specific features of the present invention are shown in some drawings and not in others. This is done for convenience only as each feature may be combined with any or all of the other features in accordance with the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The embodiments of the present invention will now be described in detail with reference to the accompanying drawings. However, the present invention is not limited to the embodiments. The present invention can be modified in various forms. Thus, the embodiments of the present invention are only provided to explain more clearly the present invention to the ordinarily skilled in the art of the present invention. In the accompanying drawings, like reference numerals are used to indicate like components.

The specification may refer to “an”, “one” or “some” embodiment(s) in several locations. This does not necessarily imply that each such reference is to the same embodiment(s), or that the feature only applies to a single embodiment. Single features of different embodiments may also be combined to provide other embodiments.

As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless expressly stated otherwise. It will be further understood that the terms “includes”, “comprises”, “including” and/or “comprising” when used in this specification, specify the presence of stated features, integers, steps, operations, elements and/or components, but do not preclude the presence or addition of one or more other features integers, steps, operations, elements, components, and/or groups thereof. As used herein, the term “and/or” includes any and all combinations and arrangements of one or more of the associated listed items.

Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

The present invention relates to a method and device for selecting efficient pathway(s) by combining chemical and biochemical processes for transformation of a target molecule.

Given the transformation nature, either chemical and/or biochemical approaches could be applied based on their merits to process the target molecule. Figure 1 is a schematic of chemical process of compound A to compound B, where the processing can be performed, chemical, biochemical or by a combination of both. A desired solution would assess individual reactions at a pathway level and select a comparatively efficient approach for the considered set of reactions while adopting a different approach for different other set within a pathway.

The present invention provide a method to predict feasible pathways with higher efficacy either through chemical or biochemical approach and select optimal processing strategies adopting a hybrid solution by combining both chemical and biochemical approaches in one pathway.

In an embodiment of the present invention, a method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule is disclosed.

The flow diagram as given in Figure 2 provides detailed steps of the present method, according to the embodiment.

Input of pathway(s) for the synthesis or degradation of target molecule(s) is received at step 202. The pathway(s) comprise sequential arrangement of the reaction step(s) resulting in synthesis of a target molecule by transforming start molecule to the target molecule or degradation of a target molecule in a desired manner. As discussed earlier, the reaction step(s) forming the pathway(s) can be either a chemical reaction step performed by chemical process or biochemical reaction step performed by biochemical process.

The number of the pathway(s) received is determined at step 204. It is checked that whether the number of pathway(s) received is only one or more than one and based on the determined number further appropriate steps are taken.

If the determined number of the pathway(s) received as the input equals to one, then a plurality of permutations in hybrid arrangement of the reaction step(s) of the received pathway are predicted at step 206. Each of the reaction step(s) in the received pathway could be a biochemical step performed by biochemical process or a chemical step performed by chemical process. For example, if the input pathway has 3 reaction steps (A?B?C?D), then there are 5 ways in which the 3 reaction steps could be arranged in hybrid fashion.

The knowledgebase comprises biochemical reaction(s), chemical reaction(s), information regarding thermodynamic feasibility or/and kinetic feasibility of the biochemical reaction(s) or/and chemical reaction(s), information regarding catalyst information or/and yield for each of the biochemical reaction(s) and chemical reaction(s). Data forming the knowledgebase serves as a reference point for analyzing the reaction steps on the aforementioned three parameters.

Reaction feasibility score is computed for each of the reaction steps of the predicted plurality of hybrid arrangement of the received pathway with reference to a knowledgebase at step 208. The reaction feasibility score is computed based on following parameters: (a) yield of step, (b) distance of the reaction step from a reference reaction step available in the knowledgebase, and (c) catalyst availability. The parameter of the catalyst availability for the biochemical reaction step refers to availability of enzyme(s) related to the biochemical reaction step, while the catalyst availability for the chemical reaction step refers to availability of catalyst(s) related to the chemical reaction step.

Further, the availability of enzyme(s) related to the biochemical reaction step is assessed based on phylogenetic distance between an organism where biochemical reaction being carried out to reference organism(s) having similar or same enzyme(s). The phylogenetic distance is calculated as per the methods known in the art. The availability of catalyst(s) related to the chemical reaction step is assessed based on distance between the catalyst(s) to most similar catalyst(s).

The parameters considered for assessing reaction feasibility in the context of the invention can be understood from Table 1. The definition of parameters is specific to an embodiment, hence in other embodiments any indirect or proxy measure of the parameters can also be used.

Parameter Biochemical Chemical
Yield (Y) Yield from substrate to product based on carbon retention, post processing for essential reactions Yield of particular reaction for a given catalyst and processing condition
Reference reaction distance (S) Similarity/dissimilarity with respect to the known reactions with similar transformation Similarity/dissimilarity with respect to the known reactions with similar transformation
Catalyst availability score (C) Availability of enzyme in the organism or a related organism computed by P Availability of the catalyst
Phylogenetic distance (P) Phylogenetically close organism to source - - organism consisting of the enzyme N.A.

Table 1

The reaction feasibility score is computed by a mathematical function combining independent scores of the parameters of yield of step (Y), distance of the reaction step from a reference reaction step available in the knowledgebase (S), and catalyst availability (C) associated with an individual reaction step. The present invention employs including, but not limited to, geometric mean or weighted average or arithmetic mean of independent score of the parameters of yield of step, distance of the reaction step from a reference reaction step available in the knowledgebase, and catalyst availability associated with an individual reaction step. Feasibility of a reaction step is computed and represented as fb for a biochemical approach and fc as a chemical approach.

Once the reaction feasibility score is computed for each of the reaction steps, it becomes easy to assess each of the reaction steps from the perspective of biochemical and chemical process and subsequently to select most feasible option(s) available at hand.

Pathway feasibility score (also termed as composite pathway score) is computed for all the predicted plurality of the hybrid arrangements of the received pathway based on the computed reaction feasibility score for each of the reaction step(s) at step 210. The pathway feasibility score is computed as a mathematical function combining the reaction feasibility score for each of the reaction step(s) forming the predicted hybrid arrangements of the received pathway. The present invention employs including, but not limited to, geometric mean or weighted average or arithmetic mean of each of the reaction step(s) forming the predicted hybrid arrangements of the received pathway.

The feasibility of each of predicted plurality of the hybrid arrangements of the received pathway is assessed based on the composite pathway score. It can be understood as higher the score, more the feasibility for the particular pathway and vice versa.

All possible plurality of the hybrid arrangements of the received pathways are considered and design pertaining to the maximized score is considered as the optimal design. The objective function for composite pathway score is defined below:
Objective function: max(?(fb), ?( fc))
where: fb and fc are the reaction feasibility score for the individual reactions based on a biochemical and a chemical approach respectively.

The objective to maximize the power set of reaction feasibility through the approaches could be performed through various methods. Table 2 summarizes two embodiments in this context.

Table 2: Method to score and optimize the power set of reaction feasibility obtained through a biochemical and chemical approach:
Method Description Preference
Maximum of scores Consider the maximum of either reaction feasibility scores at each reaction step to select the approach Preferable when there is a distinct difference between the individual reaction feasibility scores by biochemical and chemical approaches
Weighted average of the individual scores Consider a weighted average of individual reaction feasibility score for each of the plurality of hybrid arrangements and consider approach having maximum value Preferable when differences between the reaction feasibility scores by biochemical and chemical approaches are closer.

Figure 3 depicts a schema for assessing processing of compound x1 to x4 through chemical and/or biochemical/bio-technology approaches. Reaction feasibility is computed for the individual approaches simultaneously through fc and fb functions, where the power set of fc and fb are an objective function to maximize score is performed. The Figure 3 represents 8 scenarios through which processing can be achieved. The scenario 1 is where the complete processing is performed through biochemical approach, while scenario 5 represents the same being performed through chemical approach. Scenarios 2, 3, 4, 6, 7, 8 are six hybrid approaches possible for the processing of compound x1 to x4. The scenario 2 is a representative hybrid approach where the first two steps are performed biochemically, while the third step is performed chemical. The scenario 3 is a representative hybrid approach where the first step is performed biochemically and the remaining two steps are performed chemically. The scenario 4 is a representative hybrid approach where the first and third steps are performed biochemically while the second step is performed chemically. The scenario 6 is a representative hybrid approach where the first and second steps are performed chemically and the third step is performed biochemically. The scenario 7 is a representative hybrid approach where the only the first step is performed chemically and second and third steps are performed biochemically. Finally, the scenario 8 is a representative hybrid approach where the first and third steps are performed chemically and second step is performed biochemically. For each of the designs (scenarios) the composite pathway score is computed based on the feasibility of reactions through function (fb and fc). Power set is created for the feasibility score of the reactions through chemical and/or biochemical and composite hybrid feasibility score for the hybrid process/scenarios. Similarly scores are computed for all the chemical and biochemical based processing of the compounds. Furthermore, the proposed invention optimizes processing by maximization of the computed scores and proposes an optimized processing design (as discussed in earlier part of the disclosure). The design corresponding to the maximized pathway composite score is selected as the optimal chemical processing design.

The plurality of the hybrid arrangements predicted for the received pathway is sorted based on the computed pathway feasibility score at step 212. The hybrid arrangements predicted for the received pathway can be sorted in increasing or decreasing order depending on user’s requirement.

The one or more of the hybrid arrangement(s) predicted for the received pathway for the synthesis or degradation of the target molecule is/are selected based on the computed pathway feasibility score at step 214. The hybrid arrangement(s) having higher pathway feasibility score are selected.

In an embodiment, the hybrid arrangement(s) of the received pathway is/are selected when their pathway feasibility score equals to/greater than a preset threshold score. In a given scenario, where scores of none of the hybrid arrangement(s) equals to/greater than the preset threshold score, then all the hybrid arrangement(s) are discarded. Alternatively, where scores of none of the hybrid arrangement(s) matches with the preset threshold score, then the hybrid arrangement having highest pathway feasibility score is selected.

Figure 4 illustrates an exemplary embodiment of chemical and biochemical based 3 step synthesis of Adipic acid from 3, 4-Dihydroxybenzonate. Chemical and biochemical feasibility for individual reaction steps within the pathway were assessed and the objective function relate was maximized. The highest pathway feasibility score (0.71) was obtained for the second hybrid arrangement of input pathway. Based on the scoring scheme (computation of reaction feasibility score and pathway feasibility score) the present invention suggests that the first two steps, conversion of 3,4-Dihydroxybenzoate to Catechol and conversion of Catechol to cis,cis – Muconic acid should be performed biochemically. The last step conversion of cis,cis – Muconic acid to adipic acid is to be performed through a chemical approach. Further, the hybrid arrangement of the received pathway selected/suggested by the present method for processing the PEP to adipic acid based on the pathway feasibility score is consistent with reports in literature (US20090305364).

Figure 5 illustrates an exemplary embodiment of 3 step synthesis of the industrially important chemical 1,3 butadiene from 5-Hydroxy-3-oxopentanoate, where chemical and biochemical feasibility for individual reactions within the pathway were assessed and the objective function relate was maximized. The highest pathway feasibility score (0.85) was obtained for the second hybrid arrangement of input pathway. Based on the scoring scheme the present invention suggests that the first step of the pathway, conversion of 5-Hydroxy-3-oxopentanoate to 3,5-Dihydroxypentanoate is preferable through a biochemical route while the last step of the pathway, conversion of 3-butane-1-ol to 1, 3-butadiene is more preferable chemically. No preference was associated with the second step of the pathway, conversion of 3, 5- Dihydroxypentanoate to 1, 3-butadiene. The hybrid arrangement of the received pathway selected/suggested by the present method for processing the 5-Hydroxy-3-oxopentanoate to 1,3 butadiene aligns with the reports from literature [US20120021478].

In another embodiment of the present invention, the method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule further includes the step of imposing a penalty for each approach transition by way of reducing the pathway feasibility score of the individual hybrid arrangement of the received pathway by a predetermined number. As we understand that the biochemical and chemical processes takes place in entirely different environments/set ups. Therefore, it is burdensome to switch from one type of process to another while carrying out the reaction steps. Every approach transition in the pathway processing adds a certain level of discomfort to the users. Concept of the penalty is introduced to balance out the discomfort added by each and every approach transition in the hybrid pathway.

In an embodiment of imposing the penalty, the penalty is imposed for every approach transition from the one type of process to another type of process in the sequential arrangement of the reaction steps.

In another embodiment of imposing the penalty, the penalty is imposed after exempting first approach transition from one type of the process to another in the sequential arrangement of the reaction steps.

In yet another embodiment of imposing the penalty, the penalty so imposed incrementally increases from lower to higher predetermined number as number of the approach transitions from the one type of process to another type increase in the sequential arrangement of the reaction steps.

In yet another embodiment of the present invention, the method for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule further includes the step of ranking the selected hybrid arrangement(s) of the received pathway based on a preset criterion. The preset criterion for ranking is pathway feasibility scores above a given threshold.

In the scenarios where the number of pathways determined at step 204 is more than one, then instead of the step 206 the present invention provides an alternative route with different set of steps which are discussed hereinafter. There could be two embodiments: first, where all the received pathways are not processed, a prior screening is done to shortlist only the efficient pathways to be processed; and second, where all the received pathways are processed.

In the first embodiment, which has a screening stage, where only few (one or more) of the received pathways are selected for further processing and rest are discarded. The pathway feasibility score for each of the input pathways is computed at step 216, when number of input pathways is more than one. At this stage, the pathway feasibility score (the composite pathway score) for all the received pathways is computed in similar fashion as described for step 210.

The input pathways are sorted based on their pathway feasibility scores at step 218. The sorting process at this stage is performed in the similar fashion as described for step 212.

One or more of the sorted pathways received as input are selected based on their pathway feasibility scores at step 220. The selection process at this stage is performed in the similar fashion as described for the step 214.

A plurality of permutations in hybrid arrangements of the biochemical and/or chemical reaction steps are predicted for each of the selected pathway(s) at step 222. The prediction for each of the selected pathways is performed in the similar fashion as described for the step 206.

The reaction feasibility score is computed for each of the reaction steps of the plurality of hybrid arrangements predicted for each of the selected pathway(s) at step 224. The reaction feasibility score is computed in similar fashion as described for step 208.

The pathway feasibility score (the composite pathway score) is computed for all the plurality of the hybrid arrangements predicted for the selected pathways based on the reaction feasibility score at step 226. The pathway feasibility score is computed in the similar fashion as described for the step 210.

The plurality of the hybrid arrangements predicted for the selected pathways are sorted based on the pathway feasibility score at step 228. The sorting is performed in the similar fashion as described for the step 212.

One or more out of the sorted hybrid arrangement predicted for the selected pathways are selected at step 230 based on the user requirements.

Further, the present embodiment, where the received pathways are more than one, can be modified to include the chemical and/or biochemical analysis of the received pathways before computing the pathway feasibility score for the input pathways as part of the screening stage. In an embodiment, after the step 104, the input of the pathways are processed to identify (a) biochemical and chemical nature of the pathways and/or (b) similarity in the reaction steps of the pathways and/or (c) similarity of the target molecules on which the pathways are working on.

Based on the processing there can be two scenarios: (a) the input pathways are either biochemical or chemical, having different reaction steps but producing the similar target molecule, or (b) the input pathways are mixture of biochemical and chemical, having different reaction steps but producing the similar target molecule.

Further to this the processing is followed by step of screening as described for the step 216.

Further, in the scenarios where the received pathways are more than one, the above described embodiments (for processing more than one received pathways) can be modified to include the chemical and/or biochemical analysis of the received pathways before computing the pathway feasibility score for the input pathways as part of the screening stage. In one embodiment, after the step 204, the input of the pathways are processed to identify (a) biochemical and chemical nature of the pathways and/or (b) similarity in the reaction steps of the pathways and/or (c) similarity of the target molecules on which the pathways are working on.

Based on the processing there can be two scenarios: (a) the input pathways are either biochemical or chemical, having different reaction steps but producing the similar target molecule, or (b) the input pathways are mixture of biochemical and chemical, having different reaction steps but producing the similar target molecule.
Further to this, the steps of 222 to 230 are performed as described previously.

Figure 6 illustrates a second (alternative) embodiment where all the received pathways are processed without any discrimination. After the step of 204, a plurality of permutations in hybrid arrangement is predicted for the reaction step(s) of the received input pathways at step 602. The prediction is performed for each of the received pathway in the similar fashion as described for the step 206.

The reaction feasibility score is computed for each of the reaction steps of the plurality of hybrid arrangements predicted for each of the received pathway(s) at step 604. The reaction feasibility score is computed in similar fashion as described for step 208.

The pathway feasibility score (the composite pathway score) is computed for all the plurality of the hybrid arrangements predicted for each of the received pathways based on the reaction feasibility score at step 606. The pathway feasibility score is computed in the similar fashion as described for the step 210.

The plurality of the hybrid arrangements predicted for all received pathways are sorted based on their pathway feasibility scores at step 608. The sorting is performed in the similar fashion as described for the step 212.

One or more out of the sorted hybrid arrangements predicted for all the received pathways are selected at step 610, based on the user requirements.

The present invention also provides for devices to perform the methods disclosed in the specification.

Figure 7 is a block level diagram of a device for selecting pathway(s), by combining chemical and biochemical process(es), for synthesis or degradation of a target molecule in accordance with yet another embodiment of the present invention.

The device 700 includes processor(s) 706, and memory 702 coupled to the processor(s) 706.

The processor(s) 706, as used herein, means any type of computational circuit, such as, but not limited to, a microprocessor, a microcontroller, a complex instruction set computing microprocessor, a reduced instruction set computing microprocessor, a very long instruction word microprocessor, an explicitly parallel instruction computing microprocessor, a digital signal processor, or any other type of processing circuit, or a combination thereof.

The memory 702 includes a plurality of modules stored in the form of executable program which instructs the processor 706 to perform the method steps illustrated in Figures 2 and 6. The memory 702 has following modules: input receiving module 708, number of pathway determination module 710, hybrid arrangement prediction module 712, reaction and pathway feasibility computing module 714, sorting module 716, and selection module 718.

Computer memory elements may include any suitable memory device(s) for storing data and executable program, such as read only memory, random access memory, erasable programmable read only memory, electrically erasable programmable read only memory, hard drive, removable media drive for handling memory cards and the like. Embodiments of the present subject matter may be implemented in conjunction with program modules, including functions, procedures, data structures, and application programs, for performing tasks, or defining abstract data types or low-level hardware contexts. Executable program stored on any of the above-mentioned storage media may be executable by the processor(s) 706.

The input receiving module 708 instructs the processor(s) 706 to perform the step 202 (Figures 2 and 6).

The number of pathway determination module 710 instructs the processor(s) 706 to perform the step 204 (Figures 2 and 6).

The hybrid arrangement prediction module 712 instructs the processor(s) 706 to perform the steps 206 and 222 (Figure 2).

In another embodiment of the device, the hybrid arrangement prediction module 712 instructs the processor(s) 706 to perform the steps 206 and 602 (Figure 6).

The reaction and pathway feasibility computing module 714 instructs the processor(s) 706 to perform the steps 208, 210, 216, 224 and 226 (Figure 2).

In another embodiment of the device, the reaction and pathway feasibility computing module 714 instructs the processor(s) 706 to perform the steps 208, 210, 604 and 606 (Figure 6).
The sorting module 716 instructs the processor(s) 706 to perform the steps 212, 218 and 228 (Figure 2).

In another embodiment of the device, the sorting module 716 instructs the processor(s) 706 to perform the steps 212 and 608 (Figure 6).

The selection module 718 instructs the processor(s) 706 to perform the steps 214, 220 and 230 (Figure 2).

In another embodiment of the device, the selection module 718 instructs the processor(s) 706 to perform the steps 214 and 610 (Figure 6).

The present embodiments have been described with reference to specific example embodiments; it will be evident that various modifications and changes may be made to these embodiments without departing from the broader spirit and scope of the various embodiments. Furthermore, the various devices, modules, and the like described herein may be enabled and operated using hardware circuitry, for example, complementary metal oxide semiconductor based logic circuitry, firmware, software and/or any combination of hardware, firmware, and/or software embodied in a machine readable medium.