Multidimensional heuristic process for high-yield production of astaxanthin and fragrance molecules in Escherichia coli

Nature Communications
Congqiang ZhangHeng-Phon Too

Abstract

Optimization of metabolic pathways consisting of large number of genes is challenging. Multivariate modular methods (MMMs) are currently available solutions, in which reduced regulatory complexities are achieved by grouping multiple genes into modules. However, these methods work well for balancing the inter-modules but not intra-modules. In addition, application of MMMs to the 15-step heterologous route of astaxanthin biosynthesis has met with limited success. Here, we expand the solution space of MMMs and develop a multidimensional heuristic process (MHP). MHP can simultaneously balance different modules by varying promoter strength and coordinating intra-module activities by using ribosome binding sites (RBSs) and enzyme variants. Consequently, MHP increases enantiopure 3S,3'S-astaxanthin production to 184 mg l-1 day-1 or 320 mg l-1. Similarly, MHP improves the yields of nerolidol and linalool. MHP may be useful for optimizing other complex biochemical pathways.

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Citations

Jul 13, 2019·Journal of Industrial Microbiology & Biotechnology·Yuanqing WuXueming Zhao
Oct 21, 2019·Applied Microbiology and Biotechnology·Li-Qun JinYu-Guo Zheng
Aug 2, 2020·World Journal of Microbiology & Biotechnology·Quanxiu GaoBaixue Lin
Aug 31, 2018·Biotechnology for Biofuels·Jin JinYingjin Yuan
May 12, 2020·Frontiers in Bioengineering and Biotechnology·Caizhe Zhang, Kui Hong
Jul 14, 2020·Current Genomics·Zeba UsmaniRajeev Bhat
May 14, 2020·Applied Microbiology and Biotechnology·Congqiang ZhangHeng-Phon Too
Aug 18, 2020·Applied and Environmental Microbiology·Peng LiuYu-Guo Zheng
Feb 13, 2020·Current Medicinal Chemistry·Congqiang Zhang, Heng-Phon Too
Dec 30, 2020·Progress in Lipid Research·Xia WanQian-Chun Deng
Jan 8, 2020·Metabolic Engineering Communications·Cheng LiAnthony J Sinskey
Jul 8, 2021·Natural Product Reports·Mauro A RinaldiNigel S Scrutton
Dec 24, 2019·Journal of Agricultural and Food Chemistry·Xixian ChenNicholas D Lindley
May 14, 2019·Journal of Agricultural and Food Chemistry·Xixian ChenCongqiang Zhang
Dec 9, 2020·Journal of Agricultural and Food Chemistry·Zhongkuo GongXueli Zhang
Jan 8, 2021·ACS Synthetic Biology·James GilmanFilippo Menolascina
Nov 19, 2020·Journal of Agricultural and Food Chemistry·Meijie LiJianming Yang

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Methods Mentioned

BETA
PCR
flow cytometry

Software Mentioned

RBS Calculator
MHP
Alogps
MMME

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