Total Biosynthesis of Legionaminic Acid, a Bacterial Sialic Acid Analogue.

Legionaminic acid, Leg5,7Ac2 , a nonulosonic acid like 5-acetamido neuraminic acid (Neu5Ac, sialic acid), is found in cell surface glycoconjugates of bacteria including the pathogens Campylobacter jejuni, Acinetobacter baumanii and Legionella pneumophila. The presence of Leg5,7Ac2 has been correlated with virulence in humans by mechanisms that likely involve subversion of the host's immune system or interactions with host cell surfaces due to its similarity to Neu5Ac. Investigation into its role in bacterial physiology and pathogenicity is limited as there are no effective sources of it. Herein, we construct a de novo Leg5,7Ac2 biosynthetic pathway by combining multiple metabolic modules from three different microbial sources (Saccharomyces cerevisiae, C. jejuni, and L. pneumophila). Over-expression of this de novo pathway in Escherichia coli that has been engineered to lack two native catabolic pathways, enables significant quantities of Leg5,7Ac2 (≈120 mg L(-1) of culture broth) to be produced. Pure Leg5,7Ac2 could be isolated and converted into CMP-activated sugar for biochemical applications and a phenyl thioglycoside for chemical synthesis applications. This first total biosynthesis provides an essential source of Leg5,7Ac2 enabling study of its role in prokaryotic and eukaryotic glycobiology.

The Evolvability of Words: On the Nature of Lexical Items in Minimalism.

Work within the minimalist program attempts to meet the criterion of evolvability: "any mechanisms and primitives ascribed to UG rather than derived from independent factors must plausibly have emerged in what appears to have been a unique and relatively sudden event on the evolutionary timescale" (Chomsky et al., 2017). On minimalist assumptions the evolution of the language faculty must have involved at least three major developments: (i) the evolution of computational atoms, lexical items, understood as bundles of features, (ii) the evolution of a single, simple recursive operation that glues together lexical items and complexes of lexical items, and (iii) externalization linking the syntactic component of the language faculty to the cognitive systems that humans use for sound and gesture. The first development, the evolution of lexical items and the lexicon, is especially poorly understood. A complete account of the evolution of lexical items will state what evolved, how, and why. The focus of this article is the first question: what evolved. What properties do lexical items have, what determines these properties, and what is the internal structure of lexical entries? The article identifies what the key open problems are for a minimalist account of the evolution of words that strives to meet the criterion of evolvability.