Self-recycling and Partially Conservative Replication of Mycobacterial Methylmannose Polysaccharides

Overview

Journal Commun Biol

Specialty Biology

Date 2023 Jan 27

PMID 36707645

Authors

Ana Maranha

Mafalda Costa

Jorge Ripoll-Rozada

Jose A Manso

Vanessa Miranda

Vera M Mendes

Bruno Manadas

Sandra Macedo-Ribeiro

M Rita Ventura

Pedro Jose Barbosa Pereira

Nuno Empadinhas

Affiliations

Soon will be listed here.

Abstract

The steep increase in nontuberculous mycobacteria (NTM) infections makes understanding their unique physiology an urgent health priority. NTM synthesize two polysaccharides proposed to modulate fatty acid metabolism: the ubiquitous 6-O-methylglucose lipopolysaccharide, and the 3-O-methylmannose polysaccharide (MMP) so far detected in rapidly growing mycobacteria. The recent identification of a unique MMP methyltransferase implicated the adjacent genes in MMP biosynthesis. We report a wide distribution of this gene cluster in NTM, including slowly growing mycobacteria such as Mycobacterium avium, which we reveal to produce MMP. Using a combination of MMP purification and chemoenzymatic syntheses of intermediates, we identified the biosynthetic mechanism of MMP, relying on two enzymes that we characterized biochemically and structurally: a previously undescribed α-endomannosidase that hydrolyses MMP into defined-sized mannoligosaccharides that prime the elongation of new daughter MMP chains by a rare α-(1→4)-mannosyltransferase. Therefore, MMP biogenesis occurs through a partially conservative replication mechanism, whose disruption affected mycobacterial growth rate at low temperature.

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