Authors
Alexandra Márton, Josee Vandal, Vivien Bíró, Erzsébet Fekete, Erzsébet Sándor, Béla Kovács, Adrian Tsang, Levente Karaffa
Published in
Microbial cell factories. Volume 25. Issue 1. Aug 06, 2026. Epub Aug 06, 2026.
Abstract
Citric acid, a high-volume bioproduct, is manufactured by submerged fermentation using the filamentous fungus Aspergillus niger. Citric acid overflow requires Mn(II) ion concentrations not exceeding 5 µg L- 1. However, manganese easily leaches from media ingredients or stainless-steel bioreactors, necessitating costly, laborious removal.
Aspergillus niger citrate fermentations were evaluated across varied manganese profiles, comparing a novel double transporter mutant against parental and single-mutant strains. This strain overexpresses cexA - the primary plasma membrane exporter whose activity overcomes a major production bottleneck - under the control of the strong glaA promoter in a background deficient in dmtA, which encodes the primary high-affinity NRAMP-family manganese transporter. Under high-manganese conditions (100-165 µg L- 1) simulating industrial substrate impurities and bioreactor leaching, the double transporter mutant outperformed the other strains. Despite abundant manganese that triggers high biomass (50 g L- 1) and low citrate yields in the parental strain NRRL2270, this cell factory maintained high-yield overflow metabolism. Driven by an accelerated maximal glucose consumption rate of 1.61 g L- 1 h- 1 and reduced biomass accumulation (9.1 g L- 1), it accumulated citric acid to levels comparable to those achieved under manganese deficiency. The double transporter mutant compressed the fermentation period by 17% (from 300 to 250 h), minimizing operational energy and utility costs and significantly enhancing overall productivity. To validate industrial scalability, the untreated, high-manganese process was replicated in 15-L stainless steel bioreactors - accounting for up to 30 µg L- 1 of manganese leaching - and successfully scaled up by an order of magnitude in a 150-L bioreactor. Carbon balance closures within ± 5% confirmed no appreciable by-product formation.
By demonstrating the maintenance of high-yield overflow metabolism under manganese-replete conditions, alongside enhanced productivity through shortened fermentation times across different vessel scales, this study establishes this A. niger mutant as an attractive cell factory for industrial applications.
PMID:
42778925
Bibliographic data and abstract were imported from PubMed on 24 Sep 2026.
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