Methylotrophic Cell Factory as a Feasible Route for Production of High-Value Chemicals from Methanol
Methanol can be widely produced from natural gas, shale gas, CO2 as well as biomethane renewably generated from biomass, organic wastewater or biowastes via anaerobic fermentation. Therefore, methanol can be considered as an alternative abundant carbon resource for bioeconomy. Methanol-based biotechnologies using methanol-utilizing bacteria are thus of importance for production of various bioproducts. With the accumulation of knowledge and methodology for the well-known model strain of methanol-utilizing bacteria, such as Methylobacterium extorquens AM1 (AM1), a platform for design and application of methylotrophic cell factories (MeCFs) is attracting more and more attention. This chapter would summarize progress of the metabolic pathways and metabolic regulators of AM1 as the model of MeCFs and its potential for production of value-added chemicals.
This work was supported by the National Natural Science Foundation of China (NSFC 21376137) and the Tsinghua University Initiative Scientific Research Program (20131089238).
- Aldridge S (2006) Downstream processing needs a boost. Biomanufacturing trends and opportunities are meeting highlights. Gen Eng News 26:1Google Scholar
- Erb TJ, Berg IA, Brecht V, Müller M, Fuchs G, Alber BE (2007) Synthesis of C5-dicarboxylic acids from C2-units involving crotonyl-CoA carboxylase/reductase: the ethylmalonyl-CoA pathway. Proc Natl Acad Sci USA 104:10631–10636. https://doi.org/10.1073/pnas.0702791104CrossRefPubMedPubMedCentralGoogle Scholar
- Jenkins O, Jones D (1987) Taxonomic studies on some gram-negative methylotrophic bacteria. J Gen Microbiol 133:453–473Google Scholar
- Kalyuzhnaya MG, Lidstrom ME (2003) QscR, a LysR-type transcriptional regulator and CbbR homolog, is involved in regulation of the serine cycle genes in Methylobacterium extorquens AM1. J Bacteriol 185:1229–1235. https://doi.org/10.1128/JB.185.4.1229-1235.2003CrossRefPubMedPubMedCentralGoogle Scholar
- Liang W-F, Cui L-Y, Cui J-Y, Yu K-W, Yang S, Zhang C, Xing X-H (2017) Biosensor-assisted transcriptional regulator engineering for Methylobacterium extorquens AM1 to improve mevalonate synthesis by increasing the acetyl-CoA supply. Metab Eng 39:159–168. https://doi.org/10.1016/j.ymben.2016.11.010CrossRefPubMedGoogle Scholar
- Orita I, Nishikawa K, Nakamura S, Fukui T (2014) Biosynthesis of polyhydroxyalkanoate copolymers from methanol by Methylobacterium extorquens AM1 and the engineered strains under cobalt-deficient conditions. Appl Microbiol Biotechnol 98:3715–3725. https://doi.org/10.1007/s00253-013-5490-9CrossRefPubMedGoogle Scholar
- Santos CNS, Xiao W, Stephanopoulos G (2012) Rational, combinatorial, and genomic approaches for engineering L-tyrosine production in Escherichia coli. Proc Natl Acad Sci 109:13538–13543. https://doi.org/10.1073/pnas.1206346109/-/DCSupplemental.www.pnas.org/cgi/doi/10.1073/pnas.1206346109CrossRefGoogle Scholar
- Skovran E, Crowther GJ, Guo X, Yang S, Lidstrom ME (2010) A systems biology approach uncovers cellular strategies used by Methylobacterium extorquens AM1 during the switch from multi- to single-carbon growth. PLoS One 5:e14091. https://doi.org/10.1371/journal.pone.0014091CrossRefPubMedPubMedCentralGoogle Scholar
- Valdez R, Skovran E (2014) QscR regulates expression of the formate dehydrogenase genes in Methylobacterium extorquens AM1. FASEB J 28(1):946Google Scholar
- Zhu WL, Cui JY, Cui LY, Liang WF, Yang S, Zhang C, Xing XH (2016) Bioconversion of methanol to value-added mevalonate by engineered Methylobacterium extorquens AM1 containing an optimized mevalonate pathway. Appl Microbiol Biotechnol 100:2171–2182. https://doi.org/10.1007/s00253-015-7078-zCrossRefPubMedGoogle Scholar