Enzymatic carbon–sulfur bond formation in natural product biosynthesis

KL Dunbar, DH Scharf, A Litomska… - Chemical …, 2017 - ACS Publications
Sulfur plays a critical role for the development and maintenance of life on earth, which is
reflected by the wealth of primary metabolites, macromolecules, and cofactors bearing this …

[HTML][HTML] Structure of a B12-dependent radical SAM enzyme in carbapenem biosynthesis

HL Knox, EK Sinner, CA Townsend, AK Boal… - Nature, 2022 - nature.com
Carbapenems are antibiotics of last resort in the clinic. Owing to their potency and broad-
spectrum activity, they are an important part of the antibiotic arsenal. The vital role of …

Convergent biosynthetic pathways to β-lactam antibiotics

CA Townsend - Current opinion in chemical biology, 2016 - Elsevier
Highlights•The β-lactam antibiotics constitute> 60% of the antimicrobials used.•Five
evolutionarily distinct subclasses of β-lactams have evolved.•Three mechanisms of …

Consecutive radical S-adenosylmethionine methylations form the ethyl side chain in thienamycin biosynthesis

DR Marous, EP Lloyd, AR Buller… - Proceedings of the …, 2015 - National Acad Sciences
Despite their broad anti-infective utility, the biosynthesis of the paradigm carbapenem
antibiotic, thienamycin, remains largely unknown. Apart from the first two steps shared with a …

ThnL, a B12-dependent radical S-adenosylmethionine enzyme, catalyzes thioether bond formation in carbapenem biosynthesis

EK Sinner, R Li, DR Marous… - Proceedings of the …, 2022 - National Acad Sciences
Complex carbapenems are important clinical antibiotics used to treat recalcitrant infections.
Their biosynthetic gene clusters contain three essential B12-dependent radical S …

Biology and applications of co-produced, synergistic antimicrobials from environmental bacteria

KJ Meyer, JR Nodwell - Nature Microbiology, 2021 - nature.com
Environmental bacteria, such as Streptomyces spp., produce specialized metabolites that
are potent antibiotics and therapeutics. Selected specialized antimicrobials are co-produced …

Roles of 2-oxoglutarate oxygenases and isopenicillin N synthase in β-lactam biosynthesis

P Rabe, JJAG Kamps, CJ Schofield… - Natural Product …, 2018 - pubs.rsc.org
Covering: up to 2017 2-Oxoglutarate (2OG) dependent oxygenases and the homologous
oxidase isopenicillin N synthase (IPNS) play crucial roles in the biosynthesis of β-lactam ring …

Methylations in complex carbapenem biosynthesis are catalyzed by a single cobalamin-dependent radical S-adenosylmethionine enzyme

EK Sinner, MS Lichstrahl, R Li, DR Marous… - Chemical …, 2019 - pubs.rsc.org
Complex carbapenem β-lactam antibiotics contain diverse C6 alkyl substituents constructed
by cobalamin-dependent radical SAM enzymes. TokK installs the C6 isopropyl chain found …

Intraspecies comparison of Streptomyces pratensis genomes reveals high levels of recombination and gene conservation between strains of disparate geographic …

JR Doroghazi, DH Buckley - BMC genomics, 2014 - Springer
Background Streptomyces are widespread bacteria that contribute to the terrestrial carbon
cycle and produce the majority of clinically useful antibiotics. While interspecific genomic …

Structural insights into auxiliary cofactor usage by radical S-adenosylmethionine enzymes

VR Jeyachandran, AK Boal - Current opinion in chemical biology, 2022 - Elsevier
Radical S-adenosylmethionine (SAM) enzymes use a common catalytic core for diverse
transformations. While all radical SAM enzymes bind a Fe 4 S 4 cluster via a characteristic tri …