Effect of Fold-Promoting Mutation and Signal Peptide Screening on Recombinant Glucan 1,4-Alpha-maltohydrolase Secretion in Pichia pastoris

Appl Biochem Biotechnol. 2025 Jan 8. doi: 10.1007/s12010-024-05145-5. Online ahead of print.

Abstract

Glucan 1,4-alpha-maltohydrolase (3.2.1.133, GMH) is an important biocatalyst in the baking industry, which could delay the retrogradation of bread and improve its cold-storage durability. In the present study, a newly cloned Thgmh was characterized and secreted by Pichia pastoris (Komagataella pastoris). After computationally assisted rational design that promotes peptide folding, the maltogenic activity in supernatant was enhanced 1.6-fold in comparison with the base strain. The signal leading sequence screening and the gene dosage increment further improved secretion by approximately 6.4-fold. The purified rationally designed ThGMHs exhibited maximal activity against soluble starch at pH 7.0 and 60 ℃, and maltose is the main catalytic product. In a 5-L bioreactor, conventional fed-batch fermentation resulted in 6130 U mL-1 extracellular maltogenic activity. Therefore, a promising strain for GMH production was developed, which provides a useful reference for the secretory production of other industrial enzymes.

Keywords: Pichia pastoris; Fermentation; Glucan 1,4-alpha-maltohydrolase; Rational design; Signal leading sequence.