5978-70-1Relevant articles and documents
Structure of the fungal hydroxylase, CYP505A30, and rational transfer of mutation data from CYP102A1 to alter regioselectivity
Aschenbrenner, Jasmin C.,Ebrecht, Ana C.,Opperman, Diederik J.,Smit, Martha S.,Tolmie, Carmien
, p. 7359 - 7367 (2021/11/23)
CYP505A30 is a fungal, self-sufficient cytochrome P450 monooxygenase that can selectively oxyfunctionalisen-alkanes, fatty alcohols, and fatty acids. From alkanes, it produces a mixture of non-vicinal diols by two sequential hydroxylation reactions. Here we report the structure of the haem domain of CYP505A30, the first structure for a member of the CYP505 family, with dodecanoic acid bound within the active site. Overall, a high structural similarity to the related bacterial CYP102A1 was observed, despite low sequence identity (a high degree of conservation with only two amino acid differences close to the haem. Stabilisation of the fatty acid substrate in CYP505A30 also occurs, as in CYP102A1,viaan arginine residue. However, compared to R47, which is situated in the β1 region of CYP102A1, R358 is located in the β3 region of CYP505A30. We furthermore created mutants to test if it is possible to rationally transfer the knowledge on active site mutations in CYP102A1 to change the regioselectivity of CYP505A30. The introduction of F93V, I334F mutations resulted in increased ω-1 (C2) regioselectivity, similar to CYP102A1 87-328, of more than 80% forn-octane and 90% forn-decane. Changing residues to resemble the CYP102A1 wildtype increased the regioselectivity towards ω-2 (C3) to over 60% for both substrates. The knowledge gained from this study unlocks a more selective production of symmetrical non-vicinal diols fromn-alkanes.
Pickering-Droplet-Derived MOF Microreactors for Continuous-Flow Biocatalysis with Size Selectivity
Liang, Linfeng,Shi, Hu,Tian, Danping,Wang, Jun-Hao,Xue, Nan,Yang, Hengquan,Zhang, Xiaoming
supporting information, p. 16641 - 16652 (2021/10/20)
Enzymatic microarchitectures with spatially controlled reactivity, engineered molecular sieving ability, favorable interior environment, and industrial productivity show great potential in synthetic protocellular systems and practical biotechnology, but their construction remains a significant challenge. Here, we proposed a Pickering emulsion interface-directed synthesis method to fabricate such a microreactor, in which a robust and defect-free MOF layer was grown around silica emulsifier stabilized droplet surfaces. The compartmentalized interior droplets can provide a biomimetic microenvironment to host free enzymes, while the outer MOF layer secludes active species from the surroundings and endows the microreactor with size-selective permeability. Impressively, the thus-designed enzymatic microreactor exhibited excellent size selectivity and long-term stability, as demonstrated by a 1000 h continuous-flow reaction, while affording completely equal enantioselectivities to the free enzyme counterpart. Moreover, the catalytic efficiency of such enzymatic microreactors was conveniently regulated through engineering of the type or thickness of the outer MOF layer or interior environments for the enzymes, highlighting their superior customized specialties. This study provides new opportunities in designing MOF-based artificial cellular microreactors for practical applications.
Chiral Imidazo[1,5- a]pyridine-Oxazolines: A Versatile Family of NHC Ligands for the Highly Enantioselective Hydrosilylation of Ketones
Chinna Ayya Swamy,Varenikov, Andrii,Ruiter, Graham De
supporting information, p. 247 - 257 (2020/02/04)
Herein we report the synthesis and application of a versatile class of N-heterocyclic carbene ligands based on an imidazo[1,5-a]pyridine-3-ylidine backbone that is fused to a chiral oxazoline auxiliary. The key step in the synthesis of these ligands involves the installation of the oxazoline functionality via a microwave-assisted condensation of a cyano-azolium salt with a wide variety of 2-amino alcohols. The resulting chiral bidentate NHC-oxazoline ligands form stable complexes with rhodium(I) that are efficient catalysts for the enantioselective hydrosilylation of structurally diverse ketones. The corresponding secondary alcohols are isolated in good yields (typically >90%) with good to excellent enantioselectivities (80-93% ee). The reported hydrosilylation occurs at ambient temperatures (40 °C), with excellent functional group tolerability. Even ketones bearing heterocyclic substituents (e.g., pyridine or thiophene) or complex organic architectures are hydrosilylated efficiently, which is discussed further in this report.