Welcome, please Login here

Biocatalyst Development, Screening and Contract Manufacturing

  • GBP
  • USD
  • Euro

Biocatalyst Development, Screening, and Contract Manufacturing Services

Prozomix is an established supplier of maximum diversity biocatalysis enzyme panels and advanced biocatalyst discovery solutions and caters for a wide range of customers from academic synthetic chemists experimenting with green-chemistry for the first time, through to multi-project R&D programs performed for Big Pharma.  Prozomix offers the following leading-edge yet very cost-effective biocatalysis services:

(1) Custom-made Biocatalysts
(2) Lead Biocatalyst "Optimisation" Services
(3) Rational Biocatalyst Panel "Expansion" Services
(4) Prozomix Biocatalysts - "Custom Expression Vector" Services
(5) In-house Biocatalysis Enzyme Screening Services ("no hit, no fee" basis)
(6) Contract Biocatalyst (or any recombinant protein) Manufacture (from mg to multi-ton)

(For further information or any queries please contact us)

 

(1) Custom-made Biocatalysts

Projects begin from many different starting points, from customers who provide detailed technical lists of enzymes, for instance from mining the scientific literature, to those who provide just the biocatalytic activity desired (e.g. EC 1.1.1.1).  Prozomix scientists and the customer then work together to build a target list of enzymes, for which a detailed quotation containing all terms and conditions is provided.  At this stage, Prozomix works with the client to establish and avoid / manage any related IP exposure.  There is no typical project, and anywhere from 1 to 100 enzymes are either simultaneously or iteratively developed, depending on the discovery challenge in-hand.

After agreeing the final list of targets, it typically takes 4-8 weeks to produce the panel of enzymes.  This service is usually provided on an exclusive basis, depending on the class of enzyme involved, and extent of primary sequence space exploration required.  At the end of the service, the customer receives the agreed materials, which can include a crude (or pure) enzyme preparation, an expression plasmid and an expressing strain for each enzyme produced.  The final report contains all experimental details, such as a description of the final expression plasmid, expression experiments and any assay data for each member of the biocatalysis enzyme panel.

Typical costs:
US$3000 per enzyme for 1 enzyme
US$2300 per enzyme for 10 enzymes
US$1500 per enzyme for 25 or more enzymes
 
Notes:
Generally offered on a "no enzyme, no fee" basis
 
(For further information or any queries please contact us)

(2) Lead Biocatalyst "Optimisation" Services

Customers can now request a number of closely related enzymes to a lead biocatalyst be developed.  This service could especially be of value where the lead biocatalyst performs the desired transformation, but does not exhibit optimal biochemical and / or biophysical characteristics (such as thermostability, solvent tolerance, pH-activity profile, e/e, etc) for large scale commercial application.  Commonly at this stage laboratory-based protein evolution techniques such as error-prone PCR or DNA shuffling would be employed.  However, although generally effective, these techniques are frequently time consuming and expensive.  Conversely, the perpetual expansion of the Genomics database (i.e. DNA sequence information), and more recently development of Prozomix in-house proprietary meta-GRASP technology, now represents a formidable, and yet largely untapped, resource of novel enzymes for optimisation of existing biocatalysts.  This resource enables Prozomix to offer a cost-effective alternative route to "evolution-based" biocatalyst development, by way of its "Lead Biocatalyst Optimisation Services".  Essentially, this service is not a replacement for protein evolution techniques, but more establishes both rapidly and cost-effectively, whether Nature has already evolved a more effective biocatalyst than the one initially identified by the customer, that is present within the current known genome / metagenome toolkit.  With respect to this point, it is important to consider that Nature generally offers hundreds, if not thousands, or even hundreds of thousands, of enzymes within each activity class.  Of equal note, is that most of these enzymes have only been discovered in the last few years, and thus are highly likely not to be represented in any off-the-shelf kits that were developed / available some years ago.  Thus the chance that the "best" enzyme will be stumbled upon when screening some such "restricted" commercial panels is incredibly small, such as in the case of the KREDs (ketoreductases, ADHs, AKRs).  Thus a rapid answer to the question of whether a better natural enzyme exists is very valuable, as if this is the case, it could mean no protein evolution is necessary in the first place, saving much time and also cost.  Additionally, even if the more effective natural biocatalyst identified still requires in vitro evolution for the application in question, it is likely less time and cost will be involved to render it suitable, or that for the same amount of time and cost, a significantly more effective biocatalyst will result, than would have been the case beforehand.

Lead biocatalyst optimisation as described above generally requires the amino acid (primary) sequence of the lead enzyme to be known, and where such information can also be used (legally) for biocatalyst optimisation.  This may, or may not, be the case with biocatalysis enzymes purchased from some suppliers, but is always the case with biocatalysts acquired from Prozomix, either via standard off-the-shelf purchase, or by way of the "Prozomix Biocatalysis Enzyme Toolkit Concept".  Thus, where the enzyme biocatalyst to be optimised originates from Prozomix (or where the amino acid sequence is known and can be used freely), a very cost-effective service is offered, where a "sub-panel" of for example 10 enzymes can be developed within just 3-4 weeks.  For each novel biocatalyst 100 mg of freeze-dried cake / powder will then be provided to the customer for in-house evaluation against their desired applied biocatalysis application.  Generally one month is allowed for such characterisation work, after which the customer can choose as many of the novel biocatalysts as desired to take on exclusive basis (for example two), and where the remainder (for example 8) will remain the property of Prozomix, and enter the Biocatalysis Enzyme Toolkit.  For each enzyme selected by the customer, a further 1 g of freeze-dried cake / powder will be supplied, along with the expression construct (plasmid) and all expression data, etc.  The customer can then either take advantage of other related services from Prozomix, such as Contract Manufacture of the final optimal biocatalyst (see 6. below), or is totally free to use the materials supplied to achieve the same without any further reference or fee to Prozomix.   

Typical costs:
US$2500 per enzyme for the first 2 enzymes where 10 are developed
US$3500 per enzyme for the first 2 enzymes where 20 are developed
US$1500 per additional enzymes after first 2
 
Notes:
Offered on a "no enzyme, no fee" basis
 
(For further information or any queries please contact us

(3) Rational Biocatalyst Panel "Expansion" Services

For customers wishing to expand an existing, for instance in-house, biocatalyst enzyme panel, from for example initially 5 to finally 20-50 enzymes, this bespoke service option takes advantage of proprietary GRASP and more recently developed meta-GRASP platform technologies developed by Prozomix to "mine" suitable putative biocatalysts from the genomics and in-house metagenomics databases, respectively, against customer supplied criteria, and then rapidly develop them on exclusive basis.  For example, a customer may wish to add thermostable biocatalysts into their panel that likely exhibit similar substrate specificities to the original panel, and additionally select some of the novel thermotolerant enzymes to offer radically different biochemistries.

Typical costs:
US$1950 per enzyme for 5 enzymes
US$1750 per enzyme for 10 enzymes
US$1550 per enzyme for 25 enzymes
 
Notes:
Offered on a "no enzyme, no fee" basis
 
(For further information or any queries please contact us

(4) Prozomix Biocatalysts - "Custom Expression Vector" Services

Firstly, IP territory and many other historical / situational factors dictate which expression system is used by a customer, for especially large scale in-house enzyme production.  Secondly, a lead biocatalyst identified from a commercial biocatalysis enzyme kit represents an unknown with respect to in-house production using any system, presuming that expression construct development and in-house production is feasible (legally) in the first place.  Ideally then, a company would only screen biocatalysis panels produced using their own in-house expression system, as they would thus then have critical knowledge regarding expression levels and other cost factors for subsequent scaled production for identified biocatalysts already on-hand.  However, the cost of building such panels in-house or acquiring them is historically prohibitive, even for the larger user.  Such a Synthetic Chemist's ideal is, however, now possible cost-effectively from Prozomix, with specific application of its proprietary GRASP™ platform technology.  GRASP™, originally developed and used to rapidly populate the Prozomix Biocatalysis Enzyme Toolkit, can also be employed to rapidly develop derivative sets of expression plasmids based on a customer's preferred / customised expression system.  This service takes just 4 weeks, and can be followed by the additional production of 1 g of each biocatalysis enzyme using the new plasmids in a defined bacterial host, which would take an additional 4 weeks in the case of for example 100 aldo-keto reductases (ketoreductases, KREDS).  With respect to such leading-edge advanced services, the general terms of the Prozomix Biocatalysis Enzyme Toolkit Concept would also be modified accordingly, to reflect the customer's investment in the preparation of their own "ideal" biocatalysts.

For example, for the sub-cloning of 100 Prozomix aldo-keto reductases from the Prozomix Biocatalysis Enzyme Toolkit into a specific customer expression plasmid, the cost would typically be just US$10000!  For subsequent production and supply of 1 g of each enzyme as a freeze-dried cake / powder, the cost would be also just an additional US$10000!  In this case, for example, the customer would receive 100 x 1 g of enzyme preparations, and 100 x respective plasmids for subsequent in-house use.  Then according to the general Biocatalysis Enzyme Toolkit Concept Agreement, a hit fee of US$7500 would become owing to Prozomix every time an enzyme is identified and taken forward against a specific application.  However, considering the up-front investment made by the customer, the first hit fee would be waived in this instance.

Typical costs:
US$100 per plasmid for 100 plasmids developed
US$90 per plasmid for 200 plasmids developed
 
US$100 per enzyme for 100 enzymes produced
US$95 per enzyme for 200 enzymes produced
 
Notes:
(i) Amended Prozomix Biocatalysis Enzyme Toolkit Agreement to apply in favour of customer (i.e. notice period of changes to terms and conditions to be extended from 12 months to 36 months, and first hit fee to be waived)
(ii) Customer must not be a competitor, or potential competitor, of Prozomix, such evaluation to be at the sole discretion of Prozomix Directors.
 
(For further information or any queries please contact us

(5) In-house Biocatalysis Enzyme Screening Service ("no hit, no fee" basis)

For customers where acquiring and screening biocatalysis enzyme panel kits represents for instance too much of an unknown, or where time / budget does not permit, Prozomix offers an in-house Biocatalysis Enzyme Screening Service.  For example, screening of the Prozomix range of > 200 native / diverse KREDs (ketoreductases, AKRs, ADHs), is possible on a "no hit, no fee" basis.  A hit is defined and agreed between the parties ahead of screening, where the definition comprises statements on for example e/e, productivity, etc, with a particular ketone (generally supplied to Prozomix by the customer unless commercially available) in this example.  Prozomix would then screen its library of both off-the-shelf enzymes, and also other in-house private collections (including mutant libraries, etc), for a suitable catalyst(s).  If a hit is achieved within the agreed time limit, and to or beyond the agreed specification, the hit fee becomes payable, if not, no fee is payable by the customer.  This service, like all others from Prozomix, is provided on a strictly confidential basis.  In return for the hit fee, the customer receives 1 g of the biocatalyst(s) identified, along with the primary sequence of the enzyme, the expression plasmid itself, and all enzyme expression / biochemical screening data.  At this point, the customer can purchase more of the biocatalyst(s) under a Contract Manufacture agreement, or is free to produce the enzyme in-house or via any other third party without further reference or fee to Prozomix.    

Typical costs:
enquire
 
Notes:
In the case of multiple hits, assay data will be provided to the customer for each hit.  The customer can then elect to take just the "best" hit.
 
(For further information or any queries please contact us

(6) Contract Biocatalyst Manufacture (from mg to multi-ton)

Whether originating from the Prozomix Biocatalysis Enzyme Toolkit, from bespoke discovery services we perform for you, or from elsewhere, enzyme / any recombinant protein Contract Manufacture Services are available at ANY scale from Prozomix.  Where the enzyme is produced using a bacterial expression system, such as E. coli, up to 10 kg of biocatalyst powder can be produced by Prozomix per week at its site in Haltwhistle, UK.  For amounts greater than this, we would work with our scale-up partner.  The potentially unique advantage of this is that the Prozomix scale-up partner is an industrial enzyme producer, capable of multi-ton scale where necessary.  This means that with Prozomix, you have no enzyme production scaling issues when your demand rises.  Moreover, the advanced enzyme production system of our scale-up partner can be emulated at flask scale at Prozomix, meaning that even at an early stage, an indication as to whether the biocatalyst in question would be amenable to manufacture on industrial scale can be obtained for future reference.

Prozomix is currently initiating in-house research to develop an advanced continuous-flow fermentation system, that will enable it to offer between 10- and 100-fold greater quantities of GMP quality biocatalyst powders.  It is projected that this increased bulk biocatalyst offering will be available by mid 2016, and make best quality biocatalysis enzymes available at cheapest prices. 

Typical costs:
Standard list prices apply on a freeze-dried enzyme powder basis, whether the biocatalyst originated from the Prozomix enzyme collection or not.
 
 
(For further information or any queries please contact us)