From sugar uptake to bioethanol: regulation of sugar transporters in fungal cell factories

Abstract

The conversion of lignocellulosic biomass into second-generation (2G) bioethanol depends not only on efficient enzymatic hydrolysis but also on optimized microbial sugar uptake and regulation. In fungal cell factories, sugar transporters of the Major Facilitator Superfamily (MFS) represent critical engineering targets, as they govern substrate entry while simultaneously shaping intracellular signaling and carbon utilization programs. This review synthesizes current knowledge on the regulatory architecture controlling fungal sugar transporters, integrating evolutionary diversification, dual-affinity transport systems, and the coordinated uptake of hexoses and pentoses. We examine how glucose and xylose availability is translated into metabolic responses through interconnected signaling pathways, including cAMP–PKA, calcium–calcineurin, and carbon catabolite repression. Special attention is given to filamentous fungi of industrial relevance, such as Trichoderma, Aspergillus, and Neurospora, in which transporters function not only as carriers but also as transceptors that couple nutrients sensing to transcriptional control of enzyme production and central metabolism. We further discuss emerging evidence for post-translational regulation of transporters, highlighting phosphorylation-dependent mechanisms as underexplored yet promising levers for strain improvement. By consolidating regulatory principles and engineering opportunities, this review provides a framework for rational manipulation of sugar transport systems to enhance sugar co-consumption, cellulase production, and overall performance of fungal platforms for sustainable bioethanol production.