Chemo-enzymatic cascades to produce cycloalkenes from bio-based resources

Abstract

Engineered enzyme cascades offer powerful tools to convert renewable resources into valueadded products. Man-made catalysts give access to new-to-nature reactivities that may complement the enzyme's repertoire. Their mutual incompatibility, however, challenges their integration into concurrent chemo-enzymatic cascades. Herein we show that compartmentalization of complex enzyme cascades within E. coli whole cells enables the simultaneous use of a metathesis catalyst, thus allowing the sustainable one-pot production of cycloalkenes from oleic acid. Cycloheptene is produced from oleic acid via a concurrent enzymatic oxidative decarboxylation and ring-closing metathesis. Cyclohexene and cyclopentene are produced from oleic acid via either a six-or eight-step enzyme cascade involving hydration, oxidation, hydrolysis and decarboxylation, followed by ring-closing metathesis. Integration of an upstream hydrolase enables the usage of olive oil as the substrate for the production of cycloalkenes. This work highlights the potential of integrating organometallic catalysis with whole-cell enzyme cascades of high complexity to enable sustainable chemistry.

Photobiocatalytic synthesis of chiral secondary fatty alcohols from renewable unsaturated fatty acids

“…For example, with the discovery of the fatty acid decarboxylase OleT [5][6][7] or UndA/B 8 , synthesis of terminal alkenes from fatty acids has come into reach 6,[9][10][11][12] giving access to chemical building blocks 13,14 . Also the hydroxylation of fatty acids using P450 monooxygenases 15 , per-oxygenases 16,17 or dioxygenases 18 is receiving increasing attention.…”

Enhancing Biosynthesis and Manipulating Flux in Whole Cells with Abiotic Catalysis

“…Wu et al. recently combined synthetic biology with organometallic metathesis chemistry in a tour‐de‐force demonstration that yields cycloalkanes and cycloalkenes from diacids [76] . E. coli expressing a membrane‐bound desaturase‐like enzyme from Pseudomonas (UndB) decarboxylates a diacid to yield the diene, which then undergoes a (Hoveyda)‐Grubbs ruthenium(II)‐catalyzed ring closing metathesis.…”

Sustainable Chemistry – An Interdisciplinary Matrix Approach

“…Recently, a biohybrid cascade implemented in E. coli was described that was used to convert renewable resources to cycloalkenes. This was accomplished by a linear cascade that involves up to 9 enzymes together with a homogeneous Ruthenium catalyst for final conversion (ring‐closing metathesis) of the terminal diene intermediates to the corresponding cyclopentene, cyclohexene and cycloheptene products [59] …”