Artificial Starch Biosynthesis Technology： Progress， Challenges， and Prospects

doi:10.13560/j.cnki.biotech.bull.1985.2025-0941

Abstract

Abstract:

Artificial starch biosynthesis refers to an innovative process that converts raw materials such as carbon dioxide and cellulose into starch through technologies including the coupling of chemical and biological catalysis, metabolic pathway reconstruction, etc., independent of traditional plant photosynthesis. Currently, the synthesis of starch from carbon dioxide has achieved a groundbreaking breakthrough in developing a brand-new unnatural carbon sequestration pathway; the conversion of cellulose into starch has made progress in the utilization of agricultural waste; and the synthesis of starch using yeast cells has shown potential in customized production. However, all three technical pathways face common issues of high cost, low efficiency, and difficulty in scaling up. This article reviews the technical principles and achievements of carbon dioxide-based starch synthesis, the pathways and application exploration of cellulose-to-starch conversion, as well as the modification mechanisms and potential of yeast cell-based starch synthesis. It also discusses the advantages, limitations, and common challenges of different technical routes. In the future, it is necessary to rely on innovations in enzyme engineering and synthetic biology to overcome the bottlenecks of cost, efficiency, and scaling up, and promote the industrial application of artificial starch in fields such as food security guarantee and carbon neutrality realization.

Key words: artificial starch, biosynthesis, CO?, cellulose, yeast

XU Xin-xin, LI Yan-jun, ZHANG Wei, HUANG Huo-qing, LUO Hui-ying, YAO Bin. Artificial Starch Biosynthesis Technology： Progress， Challenges， and Prospects[J]. Biotechnology Bulletin, 2025, 41(11): 22-27.

Figures/Tables 1

Fig. 1 Four representative pathways in starch biosynthesis(Ⅰ) Natural starch synthesis pathways in plants, where CO₂ is fixed through the Calvin-Benson cycle in chloroplasts, which are subsequently converted into ADP-glucose by AGPase and polymerized into amylose and amylopectin by SS and SBE. (Ⅱ) Artificial cell-free chemoenzymatic starch synthesis from CO₂, in which CO₂ is first reduced electrochemically to methanol, followed by stepwise enzymatic conversion to ADP-glucose, which serves as the direct precursor for amylose and amylopectin biosynthesis. (Ⅲ) Engineered yeast-mediated starch biosynthesis pathway, where CO₂-derived acetate is metabolized through the TCA cycle, glyoxylate shunt, and gluconeogenesis to generate glucose-6-phosphate, which is redirected via heterologously expressed AGPase, SS, and SBE for intracellular starch accumulation. (Ⅳ) Bio-refining system for co-production of artificial starch and SCP from corn stover. Pretreated corn stover is enzymatically hydrolyzed into cellobiose. Cellobiose is phosphorylated into G-1-P, which is then polymerized by αGP to generate synthetic amylose. Glucose is utilized by S. cerevisiae to produce microbial protein. RuBP: Ribulose-1,5-bisphosphate; 3-PGA: 3-phosphoglycerate; GAP: glyceraldehyde-3-phosphate; F-6-P: fructose-6-phosphate; G-6-P: glucose-6-phosphate; G-1-P: glucose-1-phosphate; ADPG: adenosine diphosphate glucose; DHA: dihydroxyacetone; DHAP: dihydroxyacetone phosphate; TCA cycle: tricarboxylic acid cycle; OAA: oxaloacetate; α-KG: α-ketoglutarate; PEPCK: phosphoenolpyruvate carboxykinase; GNG: gluconeogenesis; SCP: single-cell protein; AGPase: ADP-glucose pyrophosphorylase; SS: starch synthase; SBE: starch branching enzyme; αGP: α-glucan phosphorylase.

References 29

[1]	Keeling PL, Myers AM. Biochemistry and genetics of starch synthesis [J]. Annu Rev Food Sci Technol, 2010, 1: 271-303.
[2]	Bahaji A, Li J, Sánchez-López ÁM, et al. Starch biosynthesis, its regulation and biotechnological approaches to improve crop yields [J]. Biotechnol Adv, 2014, 32(1): 87-106.
[3]	Kong XB. China must protect high-quality arable land [J]. Nature, 2014, 506(7486): 7.
[4]	Lobell DB, Gourdji SM. The influence of climate change on global crop productivity [J]. Plant Physiol, 2012, 160(4): 1686-1697.
[5]	Elliott J, Glotter M, Ruane AC, et al. Characterizing agricultural impacts of recent large-scale US droughts and changing technology and management [J]. Agric Syst, 2018, 159: 275-281.
[6]	Laudien R, Schauberger B, Gleixner S, et al. Assessment of weather-yield relations of starchy maize at different scales in Peru to support the NDC implementation [J]. Agric For Meteor, 2020, 295: 108154.
[7]	Graham AE, Ledesma-Amaro R. The microbial food revolution [J]. Nat Commun, 2023, 14: 2231.
[8]	Zheng TT, Zhang ML, Wu LH, et al. Upcycling CO₂ into energy-rich long-chain compounds via electrochemical and metabolic engineering [J]. Nat Catal, 2022, 5(5): 388-396.
[9]	Tang HT, Wu LH, Guo SY, et al. Metabolic engineering of yeast for the production of carbohydrate-derived foods and chemicals from C1-3 molecules [J]. Nat Catal, 2024, 7(1): 21-34.
[10]	Abt MR, Zeeman SC. Evolutionary innovations in starch metabolism [J]. Curr Opin Plant Biol, 2020, 55: 109-117.
[11]	Llorente B, Williams TC, Goold HD, et al. Harnessing bioengineered microbes as a versatile platform for space nutrition [J]. Nat Commun, 2022, 13: 6177.
[12]	Cai T, Sun HB, Qiao J, et al. Cell-free chemoenzymatic starch synthesis from carbon dioxide [J]. Science, 2021, 373(6562): 1523-1527.
[13]	Bar-Even A, Noor E, Lewis NE, et al. Design and analysis of synthetic carbon fixation pathways [J]. Proc Natl Acad Sci USA, 2010, 107(19): 8889-8894.
[14]	Schwander T, Schada von Borzyskowski L, Burgener S, et al. A synthetic pathway for the fixation of carbon dioxide in vitro [J]. Science, 2016, 354(6314): 900-904.
[15]	Miller TE, Beneyton T, Schwander T, et al. Light-powered CO₂ fixation in a chloroplast mimic with natural and synthetic parts [J]. Science, 2020, 368(6491): 649-654.
[16]	Kirschbaum MUF. Does enhanced photosynthesis enhance growth? Lessons learned from CO₂ enrichment studies [J]. Plant Physiol, 2011, 155(1): 117-124.
[17]	Hadadi N, Hafner J, Shajkofci A, et al. ATLAS of biochemistry: a repository of all possible biochemical reactions for synthetic biology and metabolic engineering studies [J]. ACS Synth Biol, 2016, 5(10): 1155-1166.
[18]	Erb TJ, Jones PR, Bar-Even A. Synthetic metabolism: metabolic engineering meets enzyme design [J]. Curr Opin Chem Biol, 2017, 37: 56-62.
[19]	Saithong T. A formal path inference of starch biosynthesis via mathematical modelling of metabolic changes in excess CO₂ [J]. J Comput Sci Syst Biol, 2012, 5(2): 24-37.
[20]	Liu XT, Li LQ, Zhao G, et al. Optimization strategies for CO₂ biological fixation [J]. Biotechnol Adv, 2024, 73: 108364.
[21]	Tan ZG, Li J, Hou J, et al. Designing artificial pathways for improving chemical production [J]. Biotechnol Adv, 2023, 64: 108119.
[22]	Yang X, Yuan QQ, Luo H, et al. Systematic design and in vitro validation of novel one-carbon assimilation pathways [J]. Metab Eng, 2019, 56: 142-153.
[23]	Shi ZH, Xu ZY, Rong WH, et al. Reprogramming yeast metabolism for customized starch-rich micro-grain through low-carbon microbial manufacturing [J]. Nat Commun, 2025, 16: 2784.
[24]	Hann EC, Overa S, Harland-Dunaway M, et al. A hybrid inorganic-biological artificial photosynthesis system for energy-efficient food production [J]. Nat Food, 2022, 3(6): 461-471.
[25]	Liu N, Qiao KJ, Stephanopoulos G. ¹³C metabolic flux analysis of acetate conversion to lipids by Yarrowia lipolytica [J]. Metab Eng, 2016, 38: 86-97.
[26]	Sáez-Sáez J, Wang GK, Marella ER, et al. Engineering the oleaginous yeast Yarrowia lipolytica for high-level resveratrol production [J]. Metab Eng, 2020, 62: 51-61.
[27]	Sharma J, Kumar V, Prasad R, et al. Engineering of Saccharomyces cerevisiae as a consolidated bioprocessing host to produce cellulosic ethanol: Recent advancements and current challenges [J]. Biotechnol Adv, 2022, 56: 107925.
[28]	FAO. Food outlook: biannual report on global food markets [M]. Rome: Food and Agriculture Organization of the United Nations, 2019.
[29]	Xu XX, Zhang W, You C, et al. Biosynthesis of artificial starch and microbial protein from agricultural residue [J]. Sci Bull, 2023, 68(2): 214-223.