Biocatalytic synthesis of peptidic natural products and related analogues

Dake Liu; Garret M Rubin; Dipesh Dhakal; Manyun Chen; Yousong Ding

doi:10.1016/j.isci.2021.102512

Biocatalytic synthesis of peptidic natural products and related analogues

iScience. 2021 May 4;24(5):102512. doi: 10.1016/j.isci.2021.102512. eCollection 2021 May 21.

Authors

Dake Liu¹, Garret M Rubin¹, Dipesh Dhakal¹, Manyun Chen¹, Yousong Ding¹

Affiliation

¹ Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, USA.

Abstract

Peptidic natural products (PNPs) represent a rich source of lead compounds for the discovery and development of therapeutic agents for the treatment of a variety of diseases. However, the chemical synthesis of PNPs with diverse modifications for drug research is often faced with significant challenges, including the unavailability of constituent nonproteinogenic amino acids, inefficient cyclization protocols, and poor compatibility with other functional groups. Advances in the understanding of PNP biosynthesis and biocatalysis provide a promising, sustainable alternative for the synthesis of these compounds and their analogues. Here we discuss current progress in using native and engineered biosynthetic enzymes for the production of both ribosomally and nonribosomally synthesized peptides. In addition, we highlight new in vitro and in vivo approaches for the generation and screening of PNP libraries.

Keywords: Biochemistry; Biosynthesis; Green chemistry; Organic chemistry.

Publication types

Review

Grants and funding

R35 GM128742/GM/NIGMS NIH HHS/United States