ADVERTORIAL
Enzymaster : One-stop solution for next generation biocatalysis
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For a decade now , Enzymaster has provided one-stop solutions for the development and commercialisation of innovative and sustainable enzyme catalysis technologies .
Our portfolio includes enzyme identification , enzyme panel screening , smart enzyme engineering , process development , enzyme preparation by fermentation and biocatalytic manufacturing from kg to tonne scale . In addition to these services , we offer general enzyme kits representing various enzyme classes as well as customised enzyme kits that fit to the individual biotransformation needs of our customers .
Natural enzymes are often not readily applicable in industrial processes for reasons like a lack of robustness under operating conditions , insufficient activity , and product and / or substrate inhibition . The fast discovery of novel enzymes using bioinformatic methods and directed evolution facilitated by computeraided enzyme engineering has made it possible to overcome these hurdles .
Key to the successful identification and development of commercial enzymes are the proprietary BioEngine ® and BioNavigator ® platforms . BioEngine ® is our branded directed
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Figure 1 - Sitagliptin production
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Transaminase
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Mandelic acid
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evolution toolbox with integrated computational enzyme engineering .
BioNavigator ® is a set of state‐of‐the‐art methods for computational enzyme identification , in silico activity and selectivity prediction and stability calculation under process conditions . This includes bioinformatics-driven hot spot identification , focused combinatorial library design and in silico loop design .
AI and structure‐based recombination algorithms are applied to in silico prescreening to enhance the combinatorial sequence diversity coverage beyond traditional random and site-saturation mutagenesis approaches . Based on the computational results , we construct smart and small libraries of enzyme variants , which can be conveniently screened via HPLC or GC to characterise a comprehensive range of desired properties for these
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Phenyl glycinol
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Figure 2 - Halohydrin dehalogenase Platform
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4-phenyl-2- oxazolidinone
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Mirabegron
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NH 2 variants under process conditions . This enables us to reach the biocatalytic process targets in typically only three to six rounds of combined in silico and experimental directed evolution , which corresponds to a timeline of four to eight months .
We have already developed several industrial processes employing a diverse array of enzyme classes using our enzyme engineering R & D pipeline . A recent highlight is the transaminase ( Figure 1 ) process for sitagliptin API production further expanding our ( R ) - specific transaminase platform that has previously already yielded processes for the chiral building block ( R ) - phenylethylamine and the cinacalcet intermediate ( R ) -naphtylethylamine , to mention just a few examples .
In the last two years we have also started building-up a large panel of ( S ) - specific transaminases . One application is for example the production of a rimegepant intermediate ( CAS 1373116-05-2 ).
While transaminases are still one of the most important enzyme classes for API synthesis , we have , among others , also developed processes based on halohydrin dehalogenases ( HHDHs ) like the production of the Evans auxiliary ( S ) -4-phenyl-2-oxazolidone used for the production of ezetimibe . This proceeds via enzyme-catalysed alpha-position regioselective ring-opening of styrene oxide with cyanate as the nucleophile . Furthermore , a panel of HHDHs is currently developed to enable ( chemo ) enzymatic syntheses of a series of intermediates starting from styrene oxide ( Figure 2 ). ●
Dr . Osama Mahmoud
SENIOR BUSINESS DEVELOPMENT MANAGER
ENZYMASTER k + 49 ( 0 ) 211 1582 1610 J o . mahmoud @ enzymaster . com j www . enzymaster . de
SEP / OCT 2023 SPECCHEMONLINE . COM
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