2-Hydroxyacyl-CoA lyase catalyzes acyloin condensation for one-carbon bioconversion

Nature Chemical Biology
Alexander ChouRamon Gonzalez

Abstract

Despite the potential of biotechnological processes for one-carbon (C1) bioconversion, efficient biocatalysts required for their implementation are yet to be developed. To address intrinsic limitations of native C1 biocatalysts, here we report that 2-hydroxyacyl CoA lyase (HACL), an enzyme involved in mammalian α-oxidation, catalyzes the ligation of carbonyl-containing molecules of different chain lengths with formyl-coenzyme A (CoA) to produce C1-elongated 2-hydroxyacyl-CoAs. We discovered and characterized a prokaryotic variant of HACL and identified critical residues for this newfound activity, including those supporting the hypothesized thiamine pyrophosphate-dependent acyloin condensation mechanism. The use of formyl-CoA as a C1 donor provides kinetic advantages and enables C1 bioconversion to multi-carbon products, demonstrated here by engineering an Escherichia coli whole-cell biotransformation system for the synthesis of glycolate and 2-hydroxyisobutyrate from formaldehyde and formaldehyde plus acetone, respectively. Our work establishes a new approach for C1 bioconversion and the potential for HACL-based pathways to support synthetic methylotrophy.

References

Sep 1, 1974·Journal of Bacteriology·F C NeidhardtD F Smith
Jan 1, 1981·Methods in Enzymology·J C Fong, H Schulz
Apr 16, 2003·European Journal of Biochemistry·Minne CasteelsPaul P Van Veldhoven
Apr 1, 1961·Journal of Bacteriology·G KRAKOWJ A HAYASHI
Oct 14, 2003·American Journal of Medical Genetics. Part a·C MuellerC Bay
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Aug 29, 2006·Biochimica Et Biophysica Acta·Gerbert A Jansen, Ronald J A Wanders
Mar 3, 2007·Bioinformatics·Jason S Papadopoulos, Richa Agarwala
Jul 23, 2008·Biophysical Journal·Matthew D JankowskiVassily Hatzimanikatis
Jul 4, 2009·Chembiochem : a European Journal of Chemical Biology·Michael W RingHelge B Bode
Feb 27, 2010·Microbial Cell Factories·Thore Rohwerder, Roland H Müller
Jun 22, 2010·Applied and Environmental Microbiology·Young J ChoiCarlos B Míguez
Aug 13, 2011·Nature·Clementina DellomonacoRamon Gonzalez
Aug 17, 2012·Nature·Pamela P Peralta-YahyaJay D Keasling
Sep 24, 2013·Microbial Cell Factories·Outi M KoivistoinenPeter Richard
Jan 18, 2015·Metabolic Engineering·Jonas E N MüllerJulia A Vorholt
Feb 1, 2015·Applied and Environmental Microbiology·Yu JiangSheng Yang
Mar 17, 2015·Proceedings of the National Academy of Sciences of the United States of America·Justin B SiegelDavid Baker
Sep 27, 2016·Nature Reviews. Microbiology·Nico J ClaassensJohn van der Oost
Nov 20, 2016·Science·Thomas SchwanderTobias J Erb
Jan 7, 2017·Science·James M ClomburgRamon Gonzalez
Dec 8, 2017·Current Opinion in Biotechnology·R Kyle BennettEleftherios T Papoutsakis
Feb 27, 2018·Journal of the American Chemical Society·Arturo CasiniD Benjamin Gordon
May 23, 2018·Nucleic Acids Research·Andrew WaterhouseTorsten Schwede

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Citations

Apr 14, 2020·Biotechnology Journal·Arvin Y Chen, Ethan I Lan
Jul 14, 2020·Biotechnology and Bioengineering·Sebastian WenkArren Bar-Even
Jul 19, 2020·World Journal of Microbiology & Biotechnology·Philibert Tuyishime, Jean Paul Sinumvayo
Nov 2, 2019·Trends in Biotechnology·Benjamin M Woolston
Aug 24, 2020·Trends in Biotechnology·Anh Duc Nguyen, Eun Yeol Lee
Jan 11, 2021·Current Opinion in Biotechnology·Constantinos Katsimpouras, Gregory Stephanopoulos
Mar 7, 2021·International Journal of Molecular Sciences·Qiaoyu YangHuifeng Jiang
Aug 4, 2021·Nature Reviews. Microbiology·José Montaño LópezJosé L Avalos
Sep 7, 2021·ACS Catalysis·Maren NattermannTobias J Erb

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Methods Mentioned

BETA
PCR
gene knockout
nuclear magnetic resonance

Software Mentioned

SWISS
UCSF Chimera
MODEL
GenScript
BLASTp
HACL
Interactive Tree of Life

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