Abstract
Biocatalytic and chemoenzymatic biosynthesis are powerful methods of organic chemistry that use enzymes to execute selective reactions and allow the efficient production of organic compounds. The advantages of these approaches include high selectivity, mild reaction conditions, and the ability to work with complex substrates. The utilization of chemoenzymatic techniques for the synthesis of complicated compounds has lately increased dramatically in the area of organic chemistry. Biocatalytic technologies and modern synthetic methods are utilized synergistically in a multi-step approach to a target molecule under this paradigm. Chemoenzymatic techniques are promising for simplifying access to essential bioactive compounds because of the remarkable regio- and stereoselectivity of enzymatic transformations and the reaction diversity of modern organic chemistry. Enzyme kits may include ready-to-use, reproducible biocatalysts. Its use opens up new avenues for the synthesis of active therapeutic compounds and aids in drug development by synthesizing active components to construct scaffolds in a targeted and preparative manner. This study summarizes current breakthroughs as well as notable instances of biocatalytic and chemoenzymatic synthesis. To assist organic chemists in the use of enzymes for synthetic applications, it also provides some basic guidelines for selecting the most appropriate enzyme for a targeted reaction while keeping aspects like cofactor requirement, solvent tolerance, use of whole cell or isolated enzymes, and commercial availability in mind.
Keywords: Biocatalytic, chemoenzymatic, drug design, enzyme kits, biocatalytic scaffold, modern synthetic methods.
[http://dx.doi.org/10.1271/bbb.60.1391] [PMID: 8987584]
[http://dx.doi.org/10.1016/S0958-1669(02)00328-2] [PMID: 12323357]
[http://dx.doi.org/10.1039/C9SC05746C] [PMID: 32206264]
[http://dx.doi.org/10.1038/nchembio.1494] [PMID: 24657930]
[http://dx.doi.org/10.1002/anie.202006648] [PMID: 32558088]
[http://dx.doi.org/10.1021/acs.chemrev.1c00574] [PMID: 34846124]
[http://dx.doi.org/10.1002/bit.22077] [PMID: 18814289]
[http://dx.doi.org/10.1016/j.cogsc.2018.03.015]
[http://dx.doi.org/10.1002/anie.202001876] [PMID: 32330347]
[http://dx.doi.org/10.1002/elsc.200520089]
[http://dx.doi.org/10.1021/acs.chemrev.7b00741] [PMID: 29316793]
[http://dx.doi.org/10.1038/s41570-018-0055-1]
[http://dx.doi.org/10.1021/acsmedchemlett.7b00114] [PMID: 28523096]
[http://dx.doi.org/10.1002/bit.1050] [PMID: 11257600]
[http://dx.doi.org/10.1016/S0957-4166(03)00313-6]
[http://dx.doi.org/10.1016/j.biotechadv.2015.02.015] [PMID: 25795055]
[http://dx.doi.org/10.1002/anie.200803763] [PMID: 18972473]
[http://dx.doi.org/10.1002/cssc.202102709]
[http://dx.doi.org/10.3390/biomedicines10050964] [PMID: 35625702]
[http://dx.doi.org/10.1016/j.cogsc.2022.100627]
[http://dx.doi.org/10.1016/j.cbpa.2020.01.005] [PMID: 32086167]
[http://dx.doi.org/10.1002/anie.201302195] [PMID: 24520044]
[http://dx.doi.org/10.1002/1521-3773(20020617)41:12<2008::AIDANIE2008>3.0.CO;2-4.]
[http://dx.doi.org/10.1002/anie.201708408] [PMID: 29064156]
[http://dx.doi.org/10.1111/j.1745-7270.2008.00390.x]
[http://dx.doi.org/10.1021/acscatal.1c06011]
[http://dx.doi.org/10.1038/nature08043] [PMID: 19440196]
[http://dx.doi.org/10.1021/acs.chemrev.7b00014] [PMID: 28714313]
[http://dx.doi.org/10.1016/j.biotechadv.2019.107452] [PMID: 31669138]
[http://dx.doi.org/10.3390/ijms23073605] [PMID: 35408960]
[http://dx.doi.org/10.1038/s41929-020-0447-8]
[http://dx.doi.org/10.1021/acs.accounts.0c00810] [PMID: 33600149]
[http://dx.doi.org/10.1021/ja405051f] [PMID: 23930719]
[http://dx.doi.org/10.1002/cctc.202001107] [PMID: 33381242]
[http://dx.doi.org/10.1038/131535a0]
[http://dx.doi.org/10.1002/cber.18940270364]
[http://dx.doi.org/10.1007/s12010-016-2336-9] [PMID: 27900555]
[http://dx.doi.org/10.1002/(SICI)1097-0290(19981205)60:5<534:AID-BIT3>3.0.CO;2-L] [PMID: 10099461]
[http://dx.doi.org/10.1002/anie.200600379] [PMID: 16952181]
[http://dx.doi.org/10.1073/pnas.1421566112] [PMID: 25552552]
[PMID: 2700021]
[http://dx.doi.org/10.1002/9783527620999.ch3h]
[http://dx.doi.org/10.1016/j.cbpa.2004.02.001] [PMID: 15062770]
[http://dx.doi.org/10.1039/c3np70045c] [PMID: 23934236]
[http://dx.doi.org/10.1021/ja00406a037]
[http://dx.doi.org/10.1038/nchem.2879] [PMID: 29359749]
[http://dx.doi.org/10.1021/jacs.9b09385] [PMID: 31692339]
[http://dx.doi.org/10.1021/ar7001073] [PMID: 17941701]
[http://dx.doi.org/10.1016/j.biotechadv.2007.03.002] [PMID: 17459647]
[http://dx.doi.org/10.1007/b98911] [PMID: 15791939]
[http://dx.doi.org/10.1021/acs.oprd.8b00232]
[http://dx.doi.org/10.1039/c0cc00050g] [PMID: 20461279]
[http://dx.doi.org/10.1039/B817730A] [PMID: 19109687]
[http://dx.doi.org/10.1016/j.cbpa.2018.10.003] [PMID: 30336443]
[http://dx.doi.org/10.1007/s00253-020-10585-0] [PMID: 32300853]
[http://dx.doi.org/10.1126/science.1188934] [PMID: 20558668]
[http://dx.doi.org/10.1021/acscatal.7b02686]
[http://dx.doi.org/10.1021/acs.chemrev.7b00437] [PMID: 29251912]
[http://dx.doi.org/10.1038/nchembio.1278] [PMID: 23792734]
[http://dx.doi.org/10.1021/op990101l]
[http://dx.doi.org/10.1126/science.aay8484] [PMID: 31806816]
[http://dx.doi.org/10.1093/nar/gkw1099] [PMID: 27899622]
[http://dx.doi.org/10.1093/nar/gky989] [PMID: 30365038]
[http://dx.doi.org/10.1016/j.pisc.2016.07.001] [PMID: 25900361]
[http://dx.doi.org/10.1016/j.cbpa.2019.12.006] [PMID: 31935627]
[http://dx.doi.org/10.1016/S0022-2836(05)80360-2] [PMID: 2231712]
[http://dx.doi.org/10.1093/nar/gkt282] [PMID: 23609542]
[http://dx.doi.org/10.1021/acscatal.8b04575] [PMID: 31346489]
[http://dx.doi.org/10.1002/0471250953.bi0301s42]
[http://dx.doi.org/10.1002/prot.23049] [PMID: 21671455]
[http://dx.doi.org/10.1093/molbev/msr121] [PMID: 21546353]
[http://dx.doi.org/10.1093/molbev/mst012] [PMID: 23486614]
[http://dx.doi.org/10.1093/nar/gkz966] [PMID: 31691826]
[http://dx.doi.org/10.1093/molbev/msn146] [PMID: 18614527]
[http://dx.doi.org/10.1093/gbe/evu221] [PMID: 25274566]
[http://dx.doi.org/10.1016/j.sbi.2017.07.003] [PMID: 28841430]
[http://dx.doi.org/10.1038/nrg1324] [PMID: 15143319]
[http://dx.doi.org/10.1038/s41598-020-72418-4] [PMID: 32968141]
[http://dx.doi.org/10.1016/S1074-5521(99)80033-7] [PMID: 10099128]
[http://dx.doi.org/10.1021/acscentsci.9b01112] [PMID: 31807675]
[http://dx.doi.org/10.1016/j.bbapap.2015.04.015] [PMID: 25900361]
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[http://dx.doi.org/10.1371/journal.pone.0004345] [PMID: 19190775]
[http://dx.doi.org/10.1021/acscentsci.9b00835] [PMID: 31807686]
[http://dx.doi.org/10.1128/microbiolspec.PLAS-0038-2014] [PMID: 26104560]
[http://dx.doi.org/10.1101/cshperspect.a023812] [PMID: 28049645]
[http://dx.doi.org/10.1109/TSMCC.2005.855515]
[http://dx.doi.org/10.2174/157489310794072508]
[http://dx.doi.org/10.1038/nbt.3365] [PMID: 26448090]
[http://dx.doi.org/10.1002/biot.201000332] [PMID: 21567958]
[http://dx.doi.org/10.1126/science.aaf3639] [PMID: 27540174]
[http://dx.doi.org/10.1007/978-1-4939-9877-7_28]
[http://dx.doi.org/10.1126/science.1170160] [PMID: 19359587]
[http://dx.doi.org/10.1007/s00253-002-1158-6] [PMID: 12536251]
[http://dx.doi.org/10.1016/j.cell.2016.02.004] [PMID: 26967285]
[http://dx.doi.org/10.1002/9783527824465.ch16]
[http://dx.doi.org/10.1002/9781119487043]
[http://dx.doi.org/10.1039/C0OB00353K] [PMID: 20820664]
[http://dx.doi.org/10.1016/j.cbpa.2016.11.022] [PMID: 28038349]
[http://dx.doi.org/10.1021/acscatal.1c04543]
[http://dx.doi.org/10.1038/nchem.2782] [PMID: 28937665]
[http://dx.doi.org/10.1021/jacsau.1c00251] [PMID: 34604841]
[http://dx.doi.org/10.1016/j.tibtech.2019.01.001] [PMID: 30739814]
[http://dx.doi.org/10.1002/cctc.202200156]
[http://dx.doi.org/10.1039/C5SC04027B] [PMID: 29899939]
[http://dx.doi.org/10.1039/C3SC52911H] [PMID: 25580210]
[http://dx.doi.org/10.1111/cbdd.13443] [PMID: 30485666]
[http://dx.doi.org/10.1021/acscatal.6b02979]
[http://dx.doi.org/10.1038/s41929-018-0157-7]
[http://dx.doi.org/10.1002/anie.201705976] [PMID: 28771960]
[http://dx.doi.org/10.1039/c2cs15286j] [PMID: 22234546]
[http://dx.doi.org/10.1038/nature11117] [PMID: 22575958]
[http://dx.doi.org/10.1007/978-3-642-17393-6]
[http://dx.doi.org/10.1021/acscentsci.0c01496] [PMID: 33532569]
[http://dx.doi.org/10.1016/j.tibtech.2011.06.012] [PMID: 21782265]
[http://dx.doi.org/10.1039/c3cs60011d] [PMID: 23475180]
[http://dx.doi.org/10.1126/science.166.3902.178] [PMID: 17731475]
[http://dx.doi.org/10.1021/acs.jcim.1c01074] [PMID: 35258953]
[http://dx.doi.org/10.1021/acs.accounts.9b00420] [PMID: 31714740]
[http://dx.doi.org/10.1021/acscentsci.1c00273] [PMID: 34345663]
[http://dx.doi.org/10.1016/j.eng.2022.04.021]
[http://dx.doi.org/10.1002/chem.201702235] [PMID: 28514518]
[http://dx.doi.org/10.1016/j.cbpa.2016.02.018] [PMID: 27015292]
[http://dx.doi.org/10.1021/ja809673d] [PMID: 19469578]
[http://dx.doi.org/10.1002/3527607544]
[http://dx.doi.org/10.1111/j.1574-6976.2002.tb00599.x] [PMID: 12007643]
[http://dx.doi.org/10.1021/ja0259842] [PMID: 12148986]
[http://dx.doi.org/10.1128/aem.62.9.3554-3556.1996] [PMID: 16535416]
[http://dx.doi.org/10.1007/s00253-016-7750-y] [PMID: 27502414]
[http://dx.doi.org/10.1007/s00253-016-7670-x] [PMID: 27328941]
[http://dx.doi.org/10.1016/S0040-4039(00)74673-9]
[http://dx.doi.org/10.1002/9783527629541]
[http://dx.doi.org/10.1021/ar500406s] [PMID: 25699471]
[PMID: 19894190]
[http://dx.doi.org/10.1039/c3gc40588e]
[http://dx.doi.org/10.1016/j.cbpa.2014.02.021] [PMID: 24721252]
[http://dx.doi.org/10.2174/0929867043364784] [PMID: 15279562]
[http://dx.doi.org/10.1039/C6OB00934D] [PMID: 27282284]
[http://dx.doi.org/10.1002/ejoc.201500852] [PMID: 26726292]
[http://dx.doi.org/10.1002/prac.19973390166]
[http://dx.doi.org/10.1039/C5QO00151J]
[http://dx.doi.org/10.1002/adsc.200600257]
[http://dx.doi.org/10.1016/j.copbio.2013.03.022] [PMID: 23611567]
[http://dx.doi.org/10.1073/pnas.0804348105] [PMID: 18768813]
[http://dx.doi.org/10.1021/jacs.7b02875] [PMID: 28525276]
[http://dx.doi.org/10.1038/s41467-019-11344-0]
[http://dx.doi.org/10.1038/nchembio.2421 ] [PMID: 28671684]
[http://dx.doi.org/10.1039/a909079g] [PMID: 11548049]
[http://dx.doi.org/10.1016/j.jbiotec.2012.06.001] [PMID: 22687248]
[http://dx.doi.org/10.1039/b208815k] [PMID: 12964834]
[http://dx.doi.org/10.1271/bbb.110303] [PMID: 21897027]
[http://dx.doi.org/10.1002/adsc.201900424]
[http://dx.doi.org/10.1038/s41929-019-0341-4]
[http://dx.doi.org/10.1038/s41929-021-00671-5]
[http://dx.doi.org/10.1016/j.tet.2005.08.031]
[http://dx.doi.org/10.1039/C8GC01697F]
[http://dx.doi.org/10.1002/anie.201303449] [PMID: 23913777]
[http://dx.doi.org/10.1016/j.tetlet.2014.07.004]
[http://dx.doi.org/10.1002/anie.201804592] [PMID: 30035356]
[http://dx.doi.org/10.1021/acscatal.0c00929] [PMID: 32337091]
[http://dx.doi.org/10.1002/cbic.201402550] [PMID: 25619338]
[http://dx.doi.org/10.1021/acscatal.0c02228]
[http://dx.doi.org/10.1002/anie.201707918] [PMID: 28940631]
[http://dx.doi.org/10.1038/s41570-021-00345-7] [PMID: 36747591]
[http://dx.doi.org/10.1021/jacs.9b08892] [PMID: 31518120]
[http://dx.doi.org/10.1002/anie.201910710] [PMID: 31515901]
[http://dx.doi.org/10.1021/acs.orglett.0c00109] [PMID: 32091219]
[http://dx.doi.org/10.1016/j.cbpa.2015.12.006] [PMID: 26773811]
[http://dx.doi.org/10.1021/acscatal.0c04704]
[http://dx.doi.org/10.1002/anie.202107619] [PMID: 34399441]
[http://dx.doi.org/10.1038/s41929-019-0300-0]
[http://dx.doi.org/10.1016/0091-3057(87)90176-6] [PMID: 3575379]
[http://dx.doi.org/10.1007/BF02244888] [PMID: 7871051]
[http://dx.doi.org/10.1021/acs.orglett.1c02374] [PMID: 34355569]
[http://dx.doi.org/10.1002/anie.202101228] [PMID: 33769659]
[http://dx.doi.org/10.1080/17460441.2022.2039620] [PMID: 35133222]
[http://dx.doi.org/10.1002/9780470015902.a0001399.pub3]
[http://dx.doi.org/10.1039/c2ob25122a] [PMID: 22565504]
[http://dx.doi.org/10.1056/NEJM199706123362403] [PMID: 9182213]
[http://dx.doi.org/10.1021/acs.orglett.0c00239] [PMID: 32108487]
[http://dx.doi.org/10.1002/iub.278] [PMID: 19946895]
[http://dx.doi.org/10.1016/j.mcat.2018.07.028]
[http://dx.doi.org/10.1002/adsc.201901230]
[http://dx.doi.org/10.1002/adsc.201800411]
[http://dx.doi.org/10.1021/acscentsci.1c00608] [PMID: 34963891]
[http://dx.doi.org/10.1139/b95-339]
[http://dx.doi.org/10.1016/j.tips.2008.07.004] [PMID: 18752857]
[http://dx.doi.org/10.1002/anie.201609557] [PMID: 28294491]
[http://dx.doi.org/10.1002/anie.201107446] [PMID: 22250044]
[http://dx.doi.org/10.1038/nature04640] [PMID: 16612385]
[http://dx.doi.org/10.2174/0929867013372292] [PMID: 11562272]
[http://dx.doi.org/10.1002/anie.201904102] [PMID: 31241812]
[http://dx.doi.org/10.1021/ja804159y] [PMID: 18680297]
[http://dx.doi.org/10.1021/acs.orglett.8b03670] [PMID: 30550285]
[http://dx.doi.org/10.1002/anie.201900926] [PMID: 30920120]
[http://dx.doi.org/10.1021/cr100307m] [PMID: 21830756]
[http://dx.doi.org/10.1021/acscatal.8b01220]
[http://dx.doi.org/10.1021/ja4051235] [PMID: 23808566]
[http://dx.doi.org/10.1002/cctc.201701995]
[http://dx.doi.org/10.1021/acscatal.7b03552]
[http://dx.doi.org/10.3390/catal8060238]
[http://dx.doi.org/10.1002/3527608184]
[http://dx.doi.org/10.2174/1389201020666190718165746] [PMID: 31333127]
[http://dx.doi.org/10.1002/bit.28027] [PMID: 34953086]
![Wayfinder Image](/images/wayfinder.jpg)