The aminoshikimic acid pathway in bacteria as source of precursors for the synthesis of antibacterial and antiviral compounds

Abstract

The aminoshikimic (ASA) pathway comprises a series of reactions resulting in the synthesis of 3-amino-5-hydroxybenzoic acid (AHBA), present in bacteria such as Amycolaptosis mediterranei and Streptomyces. AHBA is the precursor for synthesizing the mC7N units, the characteristic structural component of ansamycins and mitomycins antibiotics, compounds with important antimicrobial and anticancer activities. Furthermore, aminoshikimic acid, another relevant intermediate of the ASA pathway, is an attractive candidate for a precursor for oseltamivir phosphate synthesis, the most potent anti-influenza neuraminidase inhibitor treatment of both seasonal and pandemic influenza. This review discusses the relevance of the key intermediate AHBA as a scaffold molecule to synthesize diverse ansamycins and mitomycins. We describe the structure and control of the expression of the model biosynthetic cluster rif in A. mediterranei to synthesize ansamycins and review several current pharmaceutical applications of these molecules. Additionally, we discuss some relevant strategies developed for overproducing these chemicals, focusing on the relevance of the ASA pathway intermediates kanosmaine, AHAB and ASA.

Microbial diversity in camel milk from Xinjiang, China as revealed by metataxonomic analysis

“…Ansamycins are broad-spectrum antibiotics with antibacterial and antitumor activities. They work by inhibiting Hsp90 (Heat Shock Protein 90) in bacteria or tumor cells ( Escalante et al, 2021 ; Skrzypczak and Przybylski, 2022 ). Bhutia et al (2021) reported a significant positive correlation between ansamycin biosynthesis and Clostridium and Enterococcus abundance.…”

The shikimate pathway: gateway to metabolic diversity

“…Aminoshikimic acid (ASA) and 3amino-5-hydroxybenzoic acid (AHBA) Aminoshikimate (ASA, 151) and 3-amino-5-hydroxybenzoic acid (3,5-AHBA, 152) were once thought to originate from the shikimate pathway, 279 however seminal work by the Floss and Frost groups established the alternative, but parallel, aminoshikimate (ASA) pathway. While its discovery and characterization has been the subject of previous reviews, [280][281][282] this section will briey discuss key biosyntheses and enzymes known to date involved in the biosynthesis of ASA and 3,5-AHBA in the context of the archetype ansamycin molecule, the antibiotic rifamycin, from which many of the rst biosynthetic enzymes were characterized (Fig. 50).…”

The Therapeutic Potential of Hydroxycinnamic Acid Derivatives in Parkinson’s Disease: Focus on In Vivo Research Advancements

“…53 The biosynthetic pathway of hydroxycinnamic acids originates from the shikimate pathway, 54 which begins with the condensation of phosphoenolpyruvate (PEP) and erythrose-4phosphate (E4P) to form 3-deoxy-D-arabinoheptose-7-phosphate (DAHP), a step catalyzed by DAHP synthase. 55 Then, 3dehydroquinate (DHQ) synthase transforms DAHP to DHQ, which is further transformed by DHQ dehydrase into 3dehydroshikimate (DHS). NADPH-dependent shikimate dehydrogenase reduces DHS to shikimic acid.…”