Ahmad MI, Farooq S, Alhamoud Y, Li C, Zhang H (2023) Soy leghemoglobin: a review of its structure, production, safety aspects, and food applications. Trends Food Sci Technol 141:104199

Article  CAS  Google Scholar 

Ao L, Zhu L, Pang X, Xin Y, Guo Z, Zhu R, Li M, Gu Z, Guo Z, Zhang L (2024) Artificial protein XXA promotes soluble expression of human-derived Tumstatin. FF Industries 50(12):1–8

Google Scholar 

Aw R, Polizzi KM (2016) Liquid PTVA: a faster and cheaper alternative for generating multi-copy clones in Pichia pastoris. Microb Cell Fact 15:29

Article  PubMed  PubMed Central  Google Scholar 

Barrero JJ, Casler JC, Valero F, Ferrer P, Glick B (2018) An improved secretion signal enhances the secretion of model proteins from Pichia pastoris. Microb Cell Fact 17(1):161

Article  CAS  PubMed  PubMed Central  Google Scholar 

Besada-Lombana PB, Da Silva NA (2019) Engineering the early secretory pathway for increased protein secretion in Saccharomyces cerevisiae. Metab Eng 55:142–151

Article  CAS  PubMed  Google Scholar 

Capece L, Marti MA, Crespo A, Doctorovich F, Estrin DA (2006) Heme protein oxygen affinity regulation exerted by proximal effects. J Am Chem Soc 128(38):12455–12461

Article  CAS  PubMed  Google Scholar 

Chen HT, Niu YH, Zhang LX, Wang YP, Luo A, Dai ZH, Du GC, Zhao XR (2025) The optimized signal peptide and feeding strategy to enhance secretory expression of LegH in Komagataella phaffii. Process Biochem 156:255–262

Article  CAS  Google Scholar 

Chen JZ, Wang Y, Guo X, Rao D, Zhou WZ, Zheng P, Sun J, Ma Y (2020) Efficient bioproduction of 5-aminolevulinic acid, a promising biostimulant and nutrient, from renewable bioresources by engineered Corynebacterium glutamicum. Biotechnol Biofuels 13(1):41

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen L, Xue C, Su Y, Xiao G, Xu Z, Peilian W (2022) Optimization of leghemoglobin expression conditions in Pichia pastoris. Microbiol China 49(6):2050–2061

CAS  Google Scholar 

Fraser RZ, Shitut M, Agrawal P, Mendes O, Klapholz S (2018) Safety evaluation of soy leghemoglobin protein preparation derived from Pichia pastoris, intended for use as a flavor catalyst in plant-based meat. Int J Toxicol 37(3):241–262

Article  CAS  PubMed  PubMed Central  Google Scholar 

Guerrero F, Ciragan A, Iwaï H (2015) Tandem SUMO fusion vectors for improving soluble protein expression and purification. Protein Expr Purif 116:42–49

Article  CAS  PubMed  Google Scholar 

Guo Q, Li J, Wang M, Zhao M, Zhang G, Tang S, Xiong L, Gao B, Wang F, Wei D (2024) Multidimensional engineering of Saccharomyces cerevisiae for the efficient production of Heme by exploring the cytotoxicity and tolerance of Heme. Metab Eng 85:46–60

Article  CAS  PubMed  Google Scholar 

Ha-Neul B, Geun-Hyung K, Seung-Oh S (2025) Secretory production of plant heme-containing globins by recombinant yeast via precision fermentation. Foods 14(8):1422

Article  Google Scholar 

Hoffman M, Góra M, Rytka J (2003) Identification of rate-limiting steps in yeast Heme biosynthesis. Biochem Biophys Res Commun 310(4):1247–1253

Article  CAS  PubMed  Google Scholar 

Hu Q, Sun P, Yang S (2024) Optimization of heme formation conditions of leghemoglobin in Saccharomyces cerevisiae. Bull Ferment Sci Technol 53(4):222–229

Google Scholar 

Huang YY, Zhou JW, Li JH, Du GC, Chen J, Zhao XR (2024) Efficient secretory expression of leghemoglobin in Saccharomyces cerevisiae. Fermentation 10(3):146

Article  CAS  Google Scholar 

Hunter GA, Ferreira GC (2009) 5-aminolevulinate synthase: catalysis of the first step of heme biosynthesis. Cell Mol Biol 55(1):102–110

CAS  PubMed  Google Scholar 

Ishchuk OP, Frost AT, Muñiz-Paredes F, Matsumoto S, Laforge N, Eriksson NL, Martínez JL, Petranovic D (2021) Improved production of human hemoglobin in yeast by engineering hemoglobin degradation. Metab Eng 66:259–267

Article  CAS  PubMed  Google Scholar 

Jin Y, He X, Andoh-Kumi K, Fraser RZ, Lu M, Goodman RE (2018) Evaluating potential risks of food allergy and toxicity of soy leghemoglobin expressed in Pichia pastoris. Mol Nutr Food Res 62(1):1700297

Article  PubMed  Google Scholar 

Krishnamurthy P, Xie T, Fau - Schuetz JD, Schuetz JD (2007) The role of transporters in cellular Heme and porphyrin homeostasis. Pharmacol Ther 114(3):345–358

Article  CAS  PubMed  Google Scholar 

Kumar P, Chatli MK, Mehta N, Singh P, Malav OP, Verma AK (2017) Meat analogues: health promising sustainable meat substitutes. Crit Rev Food Sci Nutr 57(5):923–932

Article  CAS  PubMed  Google Scholar 

Lee HJ, Shin DJ, Nho SB, Lee KW, Kim S (2024) Metabolic engineering of Saccharomyces cerevisiae for fermentative production of heme. Biotechnol J 19(10):e202400351

Article  CAS  PubMed  Google Scholar 

Lee MJ, Chun S, Kim H, Kwon A, Jun S, Kang S, Kim P (2012) Porphyrin derivatives from a Recombinant Escherichia coli grown on chemically defined medium. J Microbiol Biotechnol 22(12):1653–1658

Article  CAS  PubMed  Google Scholar 

Li H, Zhang G, Zhou J (2019) Applications of synthetic biology in food industry. Biol Ind Technol 15(4):5–10

Lian Y, Jin L, Wang F, Zhang J, Ren Y (2024) Biosynthesis of plant-derived triterpenoid Asiatic acid in Saccharomyces cerevisiae cell factories. Bioorg Chem 153:107861

Article  CAS  PubMed  Google Scholar 

Liu F, Sun X, Zhou JW, Li J, Chen JZ, Du GC, Zhao XR (2024) Efficient biosynthesis of active hemoglobins through enhancing the import of heme in Saccharomyces cerevisiae. FEBS J 291(16):3737–3748

Article  CAS  PubMed  Google Scholar 

Liu F, Wang Y, Wang Y, Zhou J, Li J, Chen J, Du G, Zhao X (2025) Efficient synthesis of high-active multi-subunit hemoglobins through balanced expression of globins and robust heme-supply in Saccharomyces cerevisiae. Bioresour Technol 426:132387

Article  CAS  PubMed  Google Scholar 

Liu L, Martínez JL, Liu Z, Petranovic D, Nielsen J (2014) Balanced globin protein expression and heme biosynthesis improve production of human hemoglobin in Saccharomyces cerevisiae. Metab Eng 21:9–16

Article  CAS  PubMed  Google Scholar 

Liu M, Wang C, Liu B, Zhao X (2023) Optimization of expression conditions, purification and identification of the recombinant cowpea hemoglobin Lb II in Escherichia coli. Sci Technol Food Ind 44(4):163–170

Google Scholar 

Lüer C, Schauer S, Möbius K, Schulze J, Schubert W, Heinz D, Jahn D, Moser J (2005) Complex formation between glutamyl-tRNA reductase and glutamate-1-semialdehyde 2,1-aminomutase in Escherichia coli during the initial reactions of porphyrin biosynthesis. J Biol Chem 280(19):18568–18572

Article  PubMed  Google Scholar 

Mohanty AK, Wiener MC (2004) Membrane protein expression and production: effects of polyhistidine tag length and position. Protein Expr Purif 33(2):311–325

Article  CAS  PubMed  Google Scholar 

Ng DT, Brown J, Walter P (1996) Signal sequences specify the targeting route to the endoplasmic reticulum membrane. J Cell Biol 134(2):269–278

Article  CAS  PubMed  Google Scholar 

Ninagawa S, George G, Mori K (2021) Mechanisms of productive folding and endoplasmic reticulum-associated degradation of glycoproteins and non-glycoproteins. Biochimica et Biophysica Acta (BBA) 1865(3):129812

Article  CAS  Google Scholar 

Pentjuss A, Bolmanis E, Suleiko A, Didrihsone E, Suleiko A, Dubencovs K, Liepins J, Kazaks A, Vanags J (2023) Pichia pastoris growth-coupled heme biosynthesis analysis using metabolic. Sci Rep 13(1):15816

Article  CAS  PubMed  PubMed Central